rock%lighthouse%pyrdc%wubios@uunet.UU.NET (Roger Rock Rosner) (10/29/89)
***************************************************************************
TREATMENT - Table of Contents February 1989 - Vol 1, No 2
Anti-retroviral protocols
Alternating and Intermittent Doses of 2',3'-dideoxycytidine (ddC) and
AZT in Patients with Advanced HIV Disease (ACTG 050)
Alpha Interferon and Interleukin-2
AZT, Alpha Interferon, and GM-CSF
AZT in Asymptomatic HIV Infected Individuals (ACTG 019)
AZT in Hemophiliacs (ACTG 036)
AZT & GM-CSF
AZT and Interleukin-2
Betaseron (Beta Interferon) and Reduced Dose AZT in AIDS and Advanced
ARC patients
Pneumocystis carinii Pneumonia (PCP) protocols
Dapsone or Dapsone/Pyrimethamine for PCP Prophylaxis
Trimetrexate with Leucovorin Rescue for AIDS Patients with PCP and
Serious Intolerance to Approved Therapies (ATEU 039)
CMV Retinitis protocols
Foscarnet for CMV Retinitis
Toxoplasmosis protocols
Pyrimethamine and Dapsone for Toxoplasmosis
Miscellaneous protocols
HIV & Heart Disease Study
Previously covered protocols
Anti-retroviral protocols
Pneumocystis carinii Pneumonia protocols
Miscellaneous protocols
Other protocols
Anti-retroviral protocols
Pneumocystis carinii Pneumonia protocols
Miscellaneous protocols
***************************************************************************
ANTI-RETROVIRAL PROTOCOLS
----------------------------------
ALTERNATING AND INTERMITTENT DOSES OF 2',3'-DIDEOXYCYTIDINE (ddC) AND AZT IN
PATIENTS WITH ADVANCED HIV DISEASE (ACTG 050)
DESCRIPTION: This study will examine the tolerance for alternating and
intermittent regimens of zidovudine (also known as AZT) and ddC in persons
who have demonstrated true hematologic (blood system) intolerance to reduced
doses of AZT.
REQUIREMENTS: Participants must have: HIV infection confirmed by ELISA;
documented history of four or more weeks of AZT treatment (hemoglobin must
have been at least 9.5 mg/dl and granulocyte count must have been at least
1000 at the beginning of the treatment); documented history of hematologic
toxicity due to reduced dose AZT with recovery from that toxicity (recovery
from toxicity must be observable by the following lab results: an absolute
granulocyte count of more than 1000 cells/mm^3 and a hemoglobin of more than
9.5 with no transfusions given during the preceding four weeks); no
significant bilateral symptoms of peripheral neuropathy; either mild or no
bilateral signs of peripheral neuropathy (candidates with stable unilateral
neurologic deficit will not be excluded); the ability to care for most
personal needs requiring at most occasional assistance; attained at least 13
years of age (those between 13 and 18 must have written consent by parent or
legal guardian); no AZT administration within 14 days of entering the study;
and, if a woman of child-bearing potential, have a negative pregnancy test
with 30 days of entry in the study and use an effective method of birth
control during the study.
Participants must have laboratory values within certain limits: platelet
count of greater than 75,000/mm^3; calculated creatinine clearance of
greater than 50 ml/min/1.73m^2; and transaminase less than five times the
upper limit of normal.
Patients will be excluded from the study if they: have an active AIDS-
defining opportunistic infection; are receiving chronic anti-infective
therapy (other than inhaled aerosolized pentamidine as a preventive for
Pneumocystis Carinii pneumonia); have known mycobacteremia; have symptomatic
visceral Kaposi's sarcoma (KS), progression of KS within one month prior to
entry in the study or with neoplasms other than KS, basal cell carcinoma of
the skin or in-situ carcinoma of the cervix; demonstrate significant
malabsorption (a condition in which the body does not properly absorb
nutrients or drugs); are active substance (including alcohol) abusers; have
received any antiretrovirals except AZT within 30 days prior to entry (this
does not apply to AL-721, although its use is discouraged); are breast
feeding; have diabetes or are taking neurotoxic drugs.
ADMINISTRATION: Ninety-six patients who have recovered from dose-limiting
AZT toxicity (reaction) will be studied. Additional patients will be
enrolled to replace those who drop out of the study before it is finished.
All the AZT and ddC doses will be taken by mouth. The patients will be
randomly divided into six different treatment regimens.
A description of the six different groups follows:
1. Weekly Alternating. AZT is administered at 200 mg every four hours for
one week, after which AZT is stopped and ddC administration begins at 0.01
mg/kg (about 50 to 100 mg per patient depending on their weight) every four
hours for one week. After a week of the ddC regimen, AZT is again
administered for a week, then ddC again. There will be 24 consecutive
cycles, or 48 weeks, of therapy administered.
2. Weekly Alternating (higher dose of ddC). AZT is administered at 200 mg
every four hours for one week, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one week. After a
week of the ddC regimen, AZT is again administered for a week, then ddC
again. There will be 24 consecutive cycles, or 48 weeks, of therapy
administered.
3. Monthly Alternating. AZT is administered at 200 mg every four hours
for one week, after which AZT is stopped and ddC administration begins at
0.01 mg/kg every four hours for one week. After a week of the ddC regimen,
AZT is again administered for a week, then ddC again. A total of six
consecutive cycles, or 48 weeks, of therapy is administered.
4. Monthly Alternating (higher dose of ddC). AZT is administered at 200
mg every four hours for one week, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one week. After a
week of the ddC regimen, AZT is again administered for a week, then ddC
again. A total of six consecutive cycles, or 48 weeks, of therapy is
administered.
5. Weekly Intermittent (AZT only). AZT is administered at 200 mg every
four hours for one week, after which AZT is stopped and no drug is given for
one week. After a week with no drug given, AZT is again administered for a
week after which it is again stopped for one week. A total of 24
consecutive cycles, or 48 weeks, occur during the study. No ddC is given to
this group of the study.
6. Weekly Intermittent (ddC only). ddC is administered at 0.03 mg/kg
every four hours for one week, after which ddC is stopped and no drug is
given for one week. After a week with no drug given, ddC is again
administered for a week after which it is again stopped for one week. A
total of 24 consecutive cycles, or 48 weeks, occur during the study. No AZT
is given to this group of the study.
TERM: 48 weeks of treatment with four additional weeks of follow-up.
METHODOLOGY: Both AZT and ddC are potent inhibitors of HIV. (They are
Chain Terminators; see "A Layman's Guide to HIV" in the December, 1988
issue.) Both these drugs place the patient at risk for serious, but
different, side effects. Researchers hope to demonstrate through this study
that alternating the use of the two drugs will reduce the side effects while
maintaining the positive aspects of HIV inhibition.
CONTROLS: None
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Marybeth Goldin, George Washington University, (202) 994-2417
----------------------------------
ALPHA INTERFERON AND INTERLEUKIN-2
DESCRIPTION: An evaluation of the toxicity and effectiveness of the
combination of alpha interferon and interleukin-2 in the treatment of
patients with HIV infection.
REQUIREMENTS: Participants must: have evidence of HIV demonstrated by
ELISA and Western Blot or a positive culture for HIV; have a T4 cell count
of greater than or equal to 200/mm^3; be between the ages of 18 and 60; and
not have been exposed to chemotherapy, corticosteroid therapy or
experimental therapy for six weeks prior to entry. A negative pregnancy
test is required for women of child-bearing potential. All participants
must have a primary physician involved and available to communicate with NIH
staff during the study.
TERM: As an outpatient during the time it takes to gradually increase alpha
interferon doses to a maximum level, and hold the dose at maximum for two
weeks. As an inpatient, an additional 21 days of IL-2 infusion, with
outpatient follow-up visits for the next two months.
ADMINISTRATION: Alpha interferon is self-administered by the patient by
daily injection under the skin (much the same as the method used by
diabetics). Interleukin-2 is administered by injection into the vein
continuously for 21 days. There are weekly and bimonthly blood drawings and
clinic visits during the term of the study.
METHODOLOGY: Both alpha interferon and interleukin-2 are well-tolerated as
individual drugs in HIV-infected persons. Researchers are trying to
determine whether the use of both drugs simultaneously will result in
beneficial effects not seen in either when taken as single agents.
NOTES: Potential side effects of alpha interferon include flu-like
symptoms, a decrease in white cells, mental changes, gastrointestinal
disturbances, TEMPORARY hair loss, minor liver problems, and congestive
cardiomyopathy. Interleukin-2 has also been associated with some side
effects such as proteinuria, mild prolongation of PTT, fever, hepatitis,
rigors, increased incidence of bacterial infection, and eosinophilia. All
these effects improved or disappeared after discontinuation of the drugs.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------
AZT, ALPHA INTERFERON, AND GM-CSF
DESCRIPTION: This study is designed to evaluate the safety and
effectiveness of giving recombinant granulocyte-macrophage colony
stimulating factor (GM-CSF) in combination with AZT and alpha interferon in
patients with HIV infection.
REQUIREMENTS: Participants must: be over age 18; have a CD4 count of 200
to 500 per cubic millimeter; be positive for HIV on both the ELISA and the
Western Blot; have good veins; and be under the care of a physician with
whom the researchers can communicate while they are on the study. People
with active opportunistic infections are excluded.
TERM: Sixteen weeks after the dosages have stabilized, all of which is
outpatient.
ADMINISTRATION: Newly enrolled patients will be divided into two groups.
One group will receive 100 mg of AZT orally every four hours for four weeks,
and then will begin on interferon with 10 million units/day by injection
under the skin with the dose escalating by five million units/day every two
weeks. When the granulocyte count falls below 1000/mm^3, GM-CSF will be
started at a dose of 1 microgram (ug) per kilogram of body weight per day
(ug/kg/day), by injection under the skin. The GM-CSF dose will be escalated
to maintain the granulocyte count over 1500/mm^3. Once the patient's
granulocyte count is stable on AZT, interferon, and GM-CSF, the patient will
be treated for 16 weeks. The second group is identical to the first, except
their starting AZT dose will be 200 mg every four hours. Enrollment will be
done sequentially--the first 10 patients will be in the first group, and the
second 10 will be in the second group.
NIH patients who have previously been on combination AZT/interferon therapy
will comprise a third group. Patients in this group will begin on AZT and
interferon at the doses at which they became granulocytopenic (low counts of
granulocytes) in the past, with GM-CSF at one ug/kg/day starting at the same
time. Doses of AZT, interferon, and GM-CSF will be escalated, as tolerated,
in an attempt to bring the patients up to an optimal dosing level of AZT 200
mg every four hours and interferon 10 million units per day. The treatment
period for the third group, once the patient's granulocyte count is
stabilized above 1500/mm^3, will also be 16 weeks.
METHODOLOGY: While studies in the laboratory and in humans have shown that
AZT and alpha interferon given together can inhibit HIV, up to 50% of
patients taking this combination of drugs develop granulocytopenia, a
potentially serious decrease in a particular infection-fighting white blood
cell known as the granulocyte. Granulocyte-macrophage colony stimulating
factor is a bone marrow growth factor that stimulates production of several
types of cells found in blood, including the granulocyte.
NOTES: Potential side effects of AZT include nausea, headaches, and anemia
that may require blood transfusion. Interferon can cause flu-like symptoms
(fevers, fatigue, muscle aches, decrease in appetite), a decrease in white
blood cell count, and mental changes, including depression, memory loss, and
difficulty concentrating. The combination of AZT and interferon has been
known to cause a decrease in granulocytes and depression of liver function.
GM-CSF can cause fever, bone pain, and flu-like symptoms in some patients.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases, Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892, (301) 496-7196
----------------------------------
AZT IN ASYMPTOMATIC HIV INFECTED INDIVIDUALS (ACTG 019)
DESCRIPTION: This study is designed to show whether AIDS and ARC can be
prevented or delayed in people infected with HIV who are still healthy. A
comparison will be made between the dose of AZT (also known as zidovudine
and Retrovir) useful in AIDS and severe ARC with a lower dose to see if the
lowered dose is still effective. This is a double-blind placebo-controlled
study, which means that 67 percent of the patients will get some dosage of
AZT and 33 percent will get no treatment at all during the course of the
study. Neither the patient nor the researchers will know who is in what
group until the study is finished.
REQUIREMENTS: To be eligible for this study, all participants must be at
least 18 years old; have HIV infection as determined by ELISA and confirmed
by Western Blot; not meet the CDC (Centers for Disease Control) definition
for either AIDS or ARC. Participants must have laboratory results within
certain limits: hemoglobin greater than 13 gm/dl (males) or 12 gm/dl
(females); absolute neutrophil count of at least 1500 cells/mm^3; platelet
count of at least 100,000 cells/mm^3; normal serum creatinine; and have SGPT
and SGOT less than 1.5 times the upper limits of normal. Women of child-
bearing potential must practice abstinence or birth control; have a negative
pregnancy test within 30 days of entry into the study; and must not be
breast feeding.
Patients will be excluded from the study who: have suffered unintentional
weight loss greater than 10 pounds or 10 percent of body weight within two
years prior to entry to the study; have had unexplained temperature above
38oC (about 100.5oF) on more than five consecutive days or on more than ten
days during any 30 day period within the two years prior to the study, or
have a current temperature higher than 37.8oC (100oF); have had drenching
night sweats within the past two years; have had unexplained diarrhea (three
or more liquid stools per day persisting for more than seven days) within
two years prior to the study or have current active diarrhea; have had oral
candida (thrush) within two years of the study; have had oral hairy
leukoplakia (white spots or patches on the tongue or cheek) at any time
prior to the study; have had herpes zoster infection (shingles) within two
years of the study; are active alcohol or drug abusers; have received
antiretroviral drugs or immunomodulators within 60 days prior to the study;
have been treated with corticosteroids within 120 days of the study; have a
history of malignancy (tumors) other than cutaneous basal cell carcinoma (a
non-malignant skin cancer) or cervical carcinoma in-situ; have significant
underlying illnesses which would impair participation in a three year study;
have hemophilia; have some degree of neurological impairment; or have had a
blood transfusion within the three months prior to entry in the study.
TERM: Continuous, possibly until 1991.
ADMINISTRATION: All treatment doses will be given by capsules taken by
mouth. Patients will be divided into three treatment groups. The first
group will receive a relatively high dose of AZT five times daily. The
second group will receive a lower dose of AZT along with a placebo five
times daily. The third group will receive only a placebo five times daily.
No patient will know which group she/he is in. Participants will be
required to visit the clinic every two weeks during the first 16 weeks of
the study, and monthly thereafter.
METHODOLOGY: Zidovudine acts as an inhibitor to the copying mechanism of
HIV. (See "A Layman's Guide to HIV" in the December, 1988 issue.) Large
doses of this medication have often resulted in adverse side effects in
patients with AIDS and severe ARC. Researchers are, through this study,
attempting to find out if doses lower than those customarily given to AIDS
and ARC patients might delay or arrest the development of these stages of
the disease in healthy HIV seropositive individuals without the negative
side effects.
NOTES: Possible side effects from AZT include: headache, muscle aches,
nausea, vomiting, anemia, lowering of the white blood cell count, and
lowering of the platelet count.
CONTROLS: This is a randomized double-blind placebo-controlled study. This
means that during the course of the study neither the patient nor the
researchers will know who is receiving Zidovudine or the placebo.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Jane Courtless, R.N., George Washington University, (202) 994-2417
----------------------------------
AZT IN HEMOPHILIACS (ACTG 036)
DESCRIPTION: This is a double-blind placebo-controlled study to determine
whether AZT (also known as zidovudine or Retrovir) will delay or alter the
progression of disease in HIV infected hemophiliacs.
REQUIREMENTS: Participants must: have HIV infection confirmed by Western
Blot; be at least 12 years old; and have been diagnosed with hemophilia, Von
Willebrand's Disease, or other coagulation-deficient disorders.
Participants must have laboratory results within certain limits:
granulocyte count of at least 1000 cells/mm^3; platelet count of a least
75,000/mm^3; hematocrit greater than 30 percent; creatinine less than or
equal to 1.5 times normal or clearance of at least 50 ml/min; and
transaminases less than or equal to five times the upper limit of normal.
Participants must also have a Karnofsky performance status of 90 (able to
carry on normal activity; minor signs or symptoms or disease), although if
this measure in impaired by hemophilia complications, a status as low as 60
will be accepted (requires occasional assistance but is able to care for
most of his/her needs).
Patients will be excluded from the study if there is a history of AIDS
defining infection or malignancy or an unexplained temperature higher than
38oC (about 100.5oF) for more than five consecutive days or on more than 10
days in any 30-day period in the two years before entering the study.
Additional exclusions are: unexplained severe diarrhea; unintentional
weight loss of more than 10 percent of body weight in the past two years;
oral hairy leukoplakia (white spots or patches on the tongue or cheek); a
history of oral candidiasis not related to antibiotics; or herpes zoster
infection within the past two years. People will also be excluded if: they
have taken antiretroviral agents (like AZT) within the last eight weeks or
immunomodulating drugs (like steroids); they have taken other experimental
therapy within three months; or if they require therapy with isoniazid or
rifampin. All participants will be required to practice effective
contraception, and pregnancy is a basis for exclusion from the study.
TERM: Up to three years
ADMINISTRATION: Participants will take orally three 100 mg capsules every
four hours for five doses per day. Half of these persons will be receiving
AZT, the other half will be receiving a harmless placebo.
METHODOLOGY: AZT acts on HIV to inhibit its replication (reproduction or
copy of itself). It is a chain terminator (see explanation in A Layman's
Guide to HIV in the December, 1988 issue).
CONTROLS: This is a double-blind, placebo-controlled study, which means 50%
of the patients will get AZT, and 50% will get none. Neither the patient
nor the researchers will know which is which during the course of the study.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Naomi Israel, George Washington University, (202) 994-4200
----------------------------------
AZT & GM-CSF
DESCRIPTION: Phase I study of AZT (Azidothymidine) combined with GM-CSF
(Granulocyte/Macrophage-Colony Stimulating Factor) in patients with AIDS or
symptomatic HIV infection.
REQUIREMENTS: All participants must be at least 18 years old and have T4
cell counts of less than 200. Participants must have either never taken
AZT, or have taken at least 600mg a day, and discontinued because of
toxicity to the patient's white blood cells. Participants who were on AZT
must be off it for at least four weeks prior to the study. All participants
must have a white blood cell count of less than 4,500 per cubic millimeter,
hemoglobin of greater than nine grams per deciliter, and neutrophil (which
are mature white blood cells) counts of less than 1,500 per cubic millimeter
if the participant has never been on AZT. All participants must have
greater than 75,000 platelets per cubic millimeter and no transfusions
within the past month. People with active opportunistic infections are
excluded from the study. No other cytotoxic or antiretrovirals may be taken
while participants are in the protocol, although prophalaxis for PCP with
either Fanzidar, Bactrim, or aerosolized Pentamidine is permitted. Women
of child-bearing potential must have a negative pregnancy test prior to the
start of the study, and be willing to use birth control measures during and
for two months after the study.
TERM: Six months, with the possibility of an extension if the patient
responds favorably to the treatment. All treatment is on an outpatient
basis from the NIH Clinical Center.
ADMINISTRATION: The AZT is given orally every four hours; the GM-CSF is
given three times a day by a self-administered injection just under the skin
(similar to the way insulin is self-injected by diabetics).
METHODOLOGY: AZT, while effective at suppressing the reproduction of HIV,
has an unfortunate side effect of supressing the production of granulocytes
and macrophages, which are types of white blood cells, within the bone
marrow. GM-CSF stimulates the production of granulocytes and macrophages,
so it is hoped that by taking GM-CSF in combination with AZT, AZT's toxic
side effects can be reduced or eliminated, or that a larger dose of AZT with
tolerable side effects will be possible.
NOTES: If the patient's white cell counts fall while he/she is in the
study, the dosage of GM-CSF will be increased (two increases only) to try to
counter the toxicity problems.
CONTROLS: None (In a Phase I study, all patients receive the actual
drugs.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. James Pluda, Building 10, Room 13N248, National institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop) (301) 496-8398
----------------------------------
AZT AND INTERLEUKIN-2
DESCRIPTION: The study will evaluate the effectiveness and toxicity of the
combination of AZT (also known as zidovudine and Retrovir) and Interleukin-2
(IL-2) in the treatment of persons with HIV infection.
REQUIREMENTS: To be eligible to participate in the study, a person must
have HIV diagnosed by ELISA and Western Blot or a positive culture. The
person must not have had any of the opportunistic infections associated with
AIDS and must have over 200 T4 cells per cubic millimeter. If the person is
receiving AZT, he/she must be able to tolerate 200 mg every four hours.
TERM: Seventeen weeks (with possible extension of therapy if significant
improvement occurs)
ADMINISTRATION: AZT alone will be given for six weeks (orally). Following
that, AZT and IL-2 will be administered for three weeks. The IL-2 will be
administered IV continuously for three weeks and this part of the study will
be done on an inpatient basis. In addition there will be weekly or biweekly
blood drawing for the duration of the study.
METHODOLOGY: Studies have demonstrated that AZT can decrease the frequency
of opportunistic infections, but it sometimes results in bone marrow
suppression. IL-2 is a drug which stimulates the immune system.
Researchers are trying to determine whether the IL-2 might reduce the side
effects of AZT, thus allowing more patients to take full doses of AZT.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------
BETASERON (BETA INTERFERON) AND REDUCED DOSE AZT IN AIDS AND ADVANCED ARC
PATIENTS
DESCRIPTION: Comparative study of high dose Betaseron, low dose Betaseron,
or placebo in combination with reduced dose AZT.
REQUIREMENTS: Patients must have: laboratory evidence of HIV infection;
either AIDS by CDC criteria or documentation of an absolute T4 count less
than 200; a reaction to AZT that requires dose reduction of AZT to 500-600
mg of AZT daily and the ability to tolerate this reduced dose; Karnofsky
status of 60 or greater (be able to take care of daily needs requiring only
occasional assistance); acceptable renal (kidney) function; acceptable
hepatic (liver) function; attained at least age 18; be available for follow-
up; and be willing to continue on reduced dose AZT at own expense.
Participants must have laboratory results within certain limits:
granulocyte count currently greater than 1000/mm^3; hemoglobin greater than
8.5 mg/dl; and platelet count greater than 50,000/mm^3. People will be
excluded if they have: ineffectively controlled opportunistic infections;
Kaposi's sarcoma requiring systemic chemotherapy; cytotoxic chemotherapy
within 30 days of the first Betaseron dose; proteinuria of 2+ or greater;
concurrent therapy with anti-virals other than AZT or Betaseron; chronic
concurrent therapy with acyclovir; prior therapy with interferon; HIV
encephalopathy (dementia); HIV wasting syndrome; pregnancy or lactation
(women with childbearing potential must take adequate precautions to prevent
pregnancy during treatment); active drug or alcohol abuse; New York heart
classification III or IV; uncontrolled angina pectoris (severe pain about
the heart, usually travelling down the left arm); or evidence of clinically
significant multifocal uncontrolled cardiac dysrhythmias.
TERM: Indefinite. The study will continue until the superiority of the
treatment is clearly demonstrated or disproved.
ADMINISTRATION: All patients continue on reduced dose AZT. Each patient is
assigned to one of three treatment groups--high dose Betaseron, low dose
Betaseron, or placebo. The patient administers daily injections of the
study drug into the skin (in the same way that diabetics inject themselves).
The patient must visit the test site for lab and physical evaluations once a
week for a month, biweekly for two months, and monthly thereafter.
METHODOLOGY: Many patients on AZT develop side effects which involve the
blood and must, therefore, be put on a reduced dose of AZT. In the
laboratory, Betaseron (a recombinant form of interferon Beta) has been shown
to enhance the action of AZT in blocking the ability of the HIV to make
copies of itself, to kill lymphocytes, and to spread between lymphocytes.
In clinical studies, patients who have taken Betaseron have shown evidence
of suppression of the HIV copying mechanism and a low incidence of
opportunistic infections. Although there may be side effects from
Betaseron, they are seldom related to the blood. As a result, researchers
believe that a level of AZT which is not toxic to the patient might be
combined with Betaseron to get positive results similar to a higher AZT dose
without the negative side effects of AZT on the blood.
NOTES: Possible side effects of Betaseron include mild flu-like symptoms
and redness at the injection site. These effects generally decrease and
disappear with continuing treatment. Sometimes a mild depression in blood
cell counts occurs.
CONTROLS: Two out of three patients will be given Betaseron, with the third
patient on a placebo. Although the study is placebo controlled, it should
be noted that all patients will be maintained on low doses of AZT, thus
ensuring that all patients will be receiving at least some anti-viral
therapy.
ORGANIZATION: George Washington University Hospital
CONTACT: Grace Gianturco, (202) 994-2417
***************************************************************************
PNEUMOCYSTIS CARINII PNEUMONIA (PCP) PROTOCOLS
----------------------------------
DAPSONE OR DAPSONE/PYRIMETHAMINE FOR PCP PROPHYLAXIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity and
efficacy of weekly dapsone or dapsone/pyrimethamine in HIV-infected persons
with prior history of PCP or who have less than 250/mm^3 CD4 cells.
REQUIREMENTS: Participants must be: 18 years of age or older; HIV
positive; and able to provide informed consent. Participants must have
either a history of documented PCP that has been successfully treated or a
CD4 count of less than 250/mm^3. Participants must be at least two weeks
from other anti-PCP prophylaxis.
TERM: One year if beneficial, or stopped if the participant develops PCP or
significant toxicity while on therapy
ADMINISTRATION: This is an outpatient study comprised of two phases. The
initial phase will consist of open dose escalation with the first five
participants receiving dapsone 100 mg orally once a week. Dose escalation
will continue in increments of 100 mg every five participants until dose-
limiting toxicity is reached in 20% of patients at a given dose. After
establishment of a tolerated dose of dapsone, pyrimethamine 25 mg will be
added. After the dose escalating phase is completed, all subsequently
entered participants will be randomized to receive either dapsone or
dapsone/pyrimethamine. Participants will be seen in the outpatient clinic
weekly for four weeks, then every two weeks for lab work and every six weeks
for nursing visits for a period of one year.
METHODOLOGY: A study of PCP in a rat model suggests that intermittent
administration of dapsone, which is a sulfone, could prevent development of
PCP. Efficacy of dapsone appears to be enhanced by a dihydrofolate
reductase inhibitor, trimethoprim, therefore it is possible that such agents
used in combination could result in improved prevention against PCP.
Pyrimethamine is a more potent agent against PCP than trimethoprim and is
effective for a longer period in the body. Combination dapsone and
pyrimethamine therapy has the advantage of being potentially well-tolerated,
easily administered, and inexpensive.
NOTES: Possible side effects include anemia, methemoglobinemia (a condition
in which the hemoglobin has been changed by a toxic substance), decreased
white blood cells, hepatitis, rash, nausea, and fatigue.
CONTROLS: None
ORGANIZATIONS: Georgetown University Hospital: Center for HIV Disease;
National Institutes of Health: National Institute of Allergy and Infectious
Diseases (NIAID)/National Cancer Institute (NCI)/Clinical Center
CONTACTS: Georgetown University Hospital (Center for HIV Disease): Dr.
James Lavelle, Georgetown University Hospital, 3800 Reservoir Road, N.W.,
Washington, DC 20007 (202) 687-8826
National Institutes of Health: Debbie Ogata-Arakaki, Building 10, Room
10D48, National Institutes of Health, Bethesda, MD 20892 (301) 496-9565
----------------------------------
TRIMETREXATE WITH LEUCOVORIN RESCUE FOR AIDS PATIENTS WITH PCP AND SERIOUS
INTOLERANCE TO APPROVED THERAPIES (ATEU 039)
DESCRIPTION: To determine the safety and efficacy of trimetrexate with
leucovorin rescue in AIDS patients with PCP who have no therapeutic
alternatives because they have demonstrated severe or life-threatening
intolerance to both pentamidine and trimethoprim/sulfamethoxazole (T/S, also
known as Bactrim).
REQUIREMENTS: Participants must: have attained at least age 12 (those
under 18 must have consent by parent or legal guardian); be HIV positive by
ELISA, HIV culture, or p24 antingemia or have a history of male homosexual
or bisexual behavior, or of intravenous drug use, or of being the recipient
of HIV-infected blood products, or of being the sexual partner of persons in
these groups; have an unequivocal diagnosis of pneumocystis carinii
pneumonia (PCP) confirmed by test; have demonstrated intolerance to both
pentamidine and trimethoprim/sulfamethoxazole (T/S, or Bactrim); and women
in the study must have a negative pregnancy test and agree to use barrier
contraception throughout the study. Participants must have laboratory
results within certain limits: serum creatinine less than or equal to 2.5
mg/dl; serum bilirubin less than or equal to three times the upper limit of
normal; serum transaminases (SGOT, SGPT) less than or equal to five times
the upper limit of normal; absolute neutrophil count greater than or equal
to 1000/mm^3; and platelet count greater than or equal to 50,000/mm^3.
People who are currently involved in other investigational therapies, or who
are breast feeding are excluded.
TERM: 24 days, all of which are inpatient.
ADMINISTRATION: Trimetrexate will be administered by vein once a day and
leucovorin by vein every six hours. The trimetrexate therapy will last for
21 days, the leucovorin therapy will last for the entire 24 days of study.
Blood tests will be taken several times a week to check for toxicity to the
medications being administered.
METHODOLOGY: Trimetrexate is a drug used to kill the organism which causes
PCP. Because trimetrexate is a very potent drug which can have negative
side effects, in this study it is given in conjunction with leucovorin,
which is a vitamin that reduces these side effects. Because PCP is a deadly
disease, those who are unable to take the two drugs which are currently
available to fight it are at great risk. Researchers hope that this
investigational treatment will provide an alternative therapy for those
patients who currently have none.
NOTES: Patients currently on AZT therapy will have to discontinue that
therapy during the 24-day duration of the study. AZT can be resumed
immediately after completion of the study.
CONTROLS: None
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Jane Courtless, R.N., George Washington University, (202) 994-2417
***************************************************************************
CMV RETINITIS PROTOCOLS
----------------------------------
FOSCARNET FOR CMV RETINITIS
DESCRIPTION: Study of the safety and effectiveness of foscarnet in AIDS
patients who have CMV retinitis.
REQUIREMENTS: This study is for people ages 18 to 60 with AIDS and a
positive HIV test who have CMV retinitis which is not immediately sight-
threatening. One or both eyes may be affected by the retinitis.
Participants must designate someone with a Durable Power of Attorney, and
must also satisfy certain laboratory conditions (serum creatinine less than
or equal to 2.0 mg/dl; neutrophil counts of greater than 1000/mm^3;
hemoglobin of greater than or equal to 8 g/dl; and platelets of greater than
25,000/mm^3). The following people are excluded: those who have been
treated with ganciclovir or foscarnet for CMV retinitis in the past; those
who are currently taking acyclovir orally or intravenously; those who have a
history of intolerance to AZT; those with corneal, lens, or vitreous
opacification which precludes fundus examination, or other retinal diseases;
and people taking other investigational drugs. Women must have a negative
pregnancy test within 14 days of the start of the study, and agree to
practice contraception for the duration of the study plus three months
afterwards.
TERM: Three weeks of inpatient treatment at the NIH Clinical Center for
those receiving foscarnet, then outpatient treatment until significant
progression of the CMV retinitis is observed. Patients who complete the
study can continue receiving foscarnet from the manufacturer at no charge
until it becomes a marketed drug.
ADMINISTRATION: Patients must undergo a physical examination including
blood tests, a chest x-ray, electrocardiogram, and tests to determine the
severity of the CMV retinitis. Patients will be randomly divided into three
groups. The first group will receive foscarnet intravenously three times a
day as inpatients at NIH for three weeks, and then once a day as
outpatients. The second group will receive the same treatment as the first
group, plus oral AZT. A third group will receive only AZT. Patients in all
groups will also receive aerosolized pentamidine to lower the risk of
Pneumocystis carinii pneumonia. Patients receiving foscarnet will have a
Hickman catheter inserted. This device is a plastic tube inserted in a
large central vein through which the drug is administered. This eliminates
the need to administer the drug into a peripheral vein each time. The tube
is placed during a simple surgical procedure performed under general
anesthesia.
Patients will be examined weekly to check for progression of the CMV
retinitis. If significant disease progression occurs in the patients
receiving only AZT, foscarnet will be made available to them.
Frequent blood testing is also required, up to 450 ml in a six-week period.
Urine tests will be taken once a week during the first three weeks, then
once every two weeks for the rest of the study.
METHODOLOGY: Foscarnet has been proven to inhibit viral activity in human
herpes viruses by interfering with the ability of the viruses to reproduce
themselves without significantly interfering with the ability of the rest of
the body's cells to reproduce. Foscarnet has been used as a treatment for
CMV in Europe, Canada, and the United States. Foscarnet also does not
appear to have the toxic effects on bone marrow that AZT does, thus giving
hope that people with CMV retinitis may have an effective treatment for this
disease without having to stop taking AZT. Ganciclovir (also known as
DHPG), the other treatment being explored for CMV retinitis, cannot be taken
at the same time as AZT. Foscarnet also has some action against HIV.
NOTES: Possible side effects of foscarnet include decreased kidney
function, confusion, inflammation of the veins, anemia, headache, fatigue,
and seizures. The Hickman catheter used for injection of the Foscarnet can
also become infected. AZT may cause decreased white blood cell counts,
making the patient more susceptible to infection, or anemia. Aerosolized
pentamidine may cause constriction of the bronchial airways.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Eye Institute/National
Institute for Allergy and Infectious Diseases
CONTACT: Dr. Judith Rubin, (301) 496-1243
***************************************************************************
TOXOPLASMOSIS PROTOCOLS
----------------------------------
PYRIMETHAMINE AND DAPSONE FOR TOXOPLASMOSIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance
and effectiveness of combination therapy with dapsone and pyrimethamine for
the treatment of central nervous system toxoplasmosis in persons with AIDS
who are resistant to or intolerant of conventional therapy.
REQUIREMENTS: Participants must: have AIDS as defined by the Centers for
Disease Control; be at least 18 years of age; be able to sign an informed
consent; and be willing to sign a durable power of attorney. Participants
must have cerebral toxoplasmosis and either have been intolerant of or
failed conventional therapy (pyrimethamine and sulfadiazine).
TERM: Life-long if therapy is beneficial. Study will be stopped if the
participant deteriorates at 14 days of therapy or fails to improve at 21
days of therapy.
ADMINISTRATION: Participants will receive oral daily doses of pyrimethamine
25 mg, dapsone 100 mg, and leucovorin 10 mg. Adjustments of pyrimethamine
and dapsone will be made if the participant fails to respond. All
participants will be admitted to the NIH Clinical Center for induction of
therapy. After seven inpatient days, participants medically stable and
reliable will be discharged to continue therapy as outpatients.
Participants will be seen in the NIH outpatient clinic weekly for the first
three weeks, and every two weeks thereafter.
METHODOLOGY: Toxoplasmosis is a life-threatening parasitic infection caused
by a protozoa, toxoplasma gondii. Pyrimethamine, a dihydrofolate reductase
inhibitor and dapsone, a sulfone agent, are known to block folic acid
metabolism, an important pathway in both humans and toxoplasma organisms.
Leucovorin, mentioned above, allows the body's cells to bypass the blockade
without affecting the anti-protozoan activity. In combination, these drugs
have the potential to be at least as effective as the conventional regimen,
pyrimethamine and sulfadiazine, but less toxic, for treatment of
toxoplasmosis.
NOTES: Possible side effects include a decrease in white blood cell count
or platelet count, anemia, methemoglobinemia, hepatitis, kidney problems,
rash, nausea, and vomiting.
CONTROLS: None
ORGANIZATION: National Institutes of Health: National Institute of Allergy
and Infectious Diseases (NIAID)/National Cancer Institute (NCI)/Clinical
Center
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892, (301) 496-9565
***************************************************************************
MISCELLANEOUS PROTOCOLS
----------------------------------
HIV & HEART DISEASE STUDY
DESCRIPTION: Long-term study of heart disease in people who are infected
with HIV.
REQUIREMENTS: Participants must be HIV positive.
TERM: The study is expected to run until June, 1993.
ADMINISTRATION: Participants will go to the study center every four months,
and will undergo three non-invasive tests of their hearts: an EKG
(electrocardiogram), an echocardiogram, and a Signal Averaged EKG (a more
sensitive, computer-processed version of the EKG). Blood will also be drawn
for analysis. Study hours are on Tuesdays, from 8:00 a.m. to 1:00 p.m. If
abnormalities are detected, participants will be asked to return every two
months.
METHODOLOGY: The EKG and other tests help analyze the condition of your
heart. The blood work checks for antibodies to heart antigens. The two
primary heart diseases being watched for are cardiomyopathy (enlargement of
the heart), and pericardial effusions (which are fluids in the sack around
the heart).
Seventy percent of AIDS patients showed cardiac problems at autopsy, many of
these problems might have been amenable to treatment with appropriate drugs.
Monitoring can help detect these types of problems early enough that they
can be treated. Many people who aren't HIV-positive but have a history of
heart disease in their family undergo this type of monitoring as a matter of
routine.
No actual treatment is performed during this study. If problems are
detected, participants are referred to their physician for treatment. Full
cooperation and access to medical records will be provided by the
researchers.
NOTES: Participants will have their results evaluated by and be seen by a
cardiologist every time they come in for testing. Confidentiality of
patient records is maintained. Copies of all testing records are sent on
request to either the participant or the participant's physician.
CONTROLS: Not applicable
ORGANIZATION: George Washington University Hospital, Division of Cardiology
CONTACT: Sara Adams, Room 2440 North, George Washington University
Hospital, 901 23rd Street, N.W., Washington, DC 20037, (202) 994-3909
***************************************************************************
PREVIOUSLY COVERED PROTOCOLS
Protocols covered in December 1988 issue of WHN:
--------------------------------------------------------------------------
ANTI-RETROVIRAL PROTOCOLS
AZT & ALPHA INTERFERON (AZT alone vs. AZT and Alpha Interferon vs. Alpha
Interferon alone, for people in the early stages of HIV infection) AZT
inteferes with replication of HIV. Alpha interferon interferes with the
final assembly process of HIV.
National Institutes of Health/National Institute of Allergy and Infectious
Diseases (NIAID), Victoria Davey, (301) 496-7196
AZT FOR VETERANS (double-blind, placebo-controlled study of patients with
ARC) AZT inteferes with replication of HIV.
Veterans Administration Hospital Medical Center, Mary Elena Seiler or Megan
Wholey, (202) 745-8694
AZT IN EARLY ARC (ATEU 016) AZT inteferes with replication of HIV.
George Washington University, Jane Courtless, (202) 994-2417
CHEMOTHERAPY AND AZIDOTHYMIDINE (AZT) WITH OR WITHOUT RADIOTHERAPY (ATEU
008) (treatment for high grade lymphoma in AIDS-risk group members) AZT
interferes with replication of HIV. Chemotherapy and radiotherapy are
standard treatments for cancer.
George Washington University, Jane Courtless, (202) 994-2417
CHEMOTHERAPY, RADIOTHERAPY AND AZT FOR AIDS-RELATED PRIMARY CENTRAL NERVOUS
SYSTEM (CNS) LYMPHOMA (ATEU 009) AZT interferes with replication of HIV.
Chemotherapy and radiotherapy are standard treatments for cancer.
George Washington University, Jane Courtless, (202) 994-2417
ddI (2',3'-DIDEOXYINOSINE) A chemical similar in action to AZT.
National Institutes of Health/National Cancer Institute, Dr. Robert
Yarchoan, (301) 496-0328
ORAL DEXTRAN SULFATE (ACTG 060) Dextran Sulfate appears to have some effect
on preventing the binding of HIV to blood cells.
George Washington University, Jane Courtless, (202) 994-2417
RECOMBINANT SOLUBLE CD4 A genetically engineered drug which mimics the
receptor for HIV and therefore competes for virus, binds it, and prevents
virus attachment to blood cells.
National Institutes of Health/National Cancer Institute, Dr. Robert
Yarchoan, (301) 496-0328
--------------------------------------------------------------------------
PNEUMOCYSTIS CARINII PNEUMONIA PROTOCOLS
AEROSOLIZED PENTAMIDINE FOR SINGLE EPISODE OF PCP Aerosolized pentamidine
helps prevent the recurrence of PCP.
Veterans Administration Hospital Medical Center, Mary Elena Seiler, (202)
745-8694
AEROSOLIZED PENTAMIDINE FOR MULTIPLE EPISODES OF PCP FOR VETERANS
Aerosolized pentamidine helps prevent the recurrence of PCP.
Veterans Administration Hospital Medical Center, Megan Wholey, (202) 745-
8694
--------------------------------------------------------------------------
MISCELLANEOUS PROTOCOLS
----------------------------------
AEROSOLIZED GAMMA-INTERFERON A Phase I study to determine drug toxicity and
effectiveness in stimulating anti-microorganism activities of lung
macrophages (white blood cells).
National Institutes of Health/National Heart, Lung, and Blood Institute,
Pulmonary Branch, (301) 496-2449
BLOOD DRAWING STUDY The blood will be used in research studies.
National Institutes of Health/National Heart, Lung, and Blood Institute,
Pulmonary Branch, (301) 496-2449
BRONCHOALVEOLAR LAVAGE STUDY Research study to determine what organisms
attack the lungs and how the lungs' defense mechanisms operate.
National Institutes of Health/National Heart, Lung, and Blood Institute,
Pulmonary Branch, (301) 496-2449
gp-160 (Trial vaccine against HIV) A genetically-engineered protein that is
part of the envelope for HIV. Hopefully, the body will develop antibodies
to gp-160 which will also be effective against HIV.
National Institutes of Health/National Institute of Allergy and Infectious
Diseases (NIAID), Margaret Easter, (301) 496-7196
--------------------------------------------------------------------------
OTHER PROTOCOLS
The following is a list of protocols, compiled by Dr. Basil Vareldzis,
Clinic Director of the Whitman-Walker Clinic, of other protocols available
in the Washington area. Future issues will carry more in-depth descriptions
of these protocols.
----------------------------------
ANTI-RETROVIRAL PROTOCOLS
ALTERNATING AND INTERMITTENT DOSES OF ddC AND AZT IN PATIENTS WITH AIDS AND
ARC (ACTG 047) Similar to ACTG050, but for AIDS and ARC patients.
George Washington University, Marybeth Goldin, (202) 994-2417
EFFECT OF AZT ON HIV ASSOCIATED NEUROLOGICAL AND/OR NEUROMUSCULAR
DYSFUNCTION
National Institutes of Health/National Institute of Mental Health, Valita
Fredland, (301) 496-2429
EFFICACY OF B12/FOLATE FOR PATIENTS ON AZT
Georgetown University, Dr. Mary Young, (202) 687-8672
NEUROPSYCHIATRIC CHANGES ACCOMPANYING ALPHA INTERFERON THERAPY IN TREATMENT
OF HIV VIREMIA
National Institutes of Health/National Institute of Mental Health, Dr. Mark
Dimitrack, (301) 496-6565
NEUROPSYCHIATRIC CHARACTERIZATION OF HIV ANTIBODY POSITIVE PERSONS ON AZT
Georgetown University, Pim Brouwers, (202) 687-4954
--------------------------------------------------------------------------
PNEUMOCYSTIS CARINII PNEUMONIA PROTOCOLS
AEROSOLIZED PENTAMIDINE: (single previous episode of PCP)
Georgetown University, Dr. Philip Pierce, (202) 687-8672
AEROSOLIZED PENTAMIDINE: (multiple episodes of PCP)
Georgetown University, Dr. Philip Pierce, (202) 687-8672
--------------------------------------------------------------------------
MISCELLANEOUS PROTOCOLS
BRAIN METABOLISM IN HIV DISEASE
National Institutes of Health/National Institute of Mental Health, Dr. Tom
Nordahl, (301) 496-4707
EVENT RELATED BRAIN POTENTIALS IN HIV DISEASE
National Institutes of Health/National Institute of Mental Health, Dr.
Christine Ollo, (301) 496-6565
MEASUREMENT OF EYE MOVEMENT IN HIV DISEASE
National Institutes of Health/National Institute of Mental Health, Dr.
Robert Litman, (301) 496-6295
NEUROPSYCHIATRIC MANIFESTATIONS OF HIV INFECTION
National Institutes of Health/National Institute of Mental Health, Dr.
Christine Ollo, (301) 496-6565
SALIVARY FUNCTION IN HIV INFECTED INDIVIDUALS
National Institutes of Health/National Institutes of Allergy and Infectious
Diseases, Dr. Yeh, (301) 496-1478
***************************************************************************
It is the intent of Washington HIV News to only list protocols which are
open to new patients. Some protocols may be on a temporary hold while the
inclusion criteria are being revised. Others, which had a projected start
date a few weeks after the publication date for this issue, were not
included because they were not actually underway and accepting patients.
Therefore, people with specific needs or interests are encouraged to call
around if they do not see a protocol listed for their needs, because
protocols may have either started or come off of hold after press time.
***************************************************************************
Copyright (C) 1988,1989 by Washington HIV News, all rights reserved.
Permission is granted for non-commercial use only.phil@wubios.WUstl.EDU (J. Philip Miller) (11/09/89)
Forwarded message:
>From pyrdc!lighthouse!rock@uunet.UU.NET Tue Oct 24 19:12:42 1989
Date: Tue, 24 Oct 89 18:54:46 GMT-0500
From: pyrdc!lighthouse!rock@uunet.UU.NET (Roger Rock Rosner)
Message-Id: <8910242354.AA01213@ lighthouse >
To: phil@wubios, ddodell@stjhmc.fidonet.org
Subject: Washington HIV News: V1N2, 1/3
***************************************************************************
TREATMENT - Table of Contents February 1989 - Vol 1, No 2
Anti-retroviral protocols
Alternating and Intermittent Doses of 2',3'-dideoxycytidine (ddC) and
AZT in Patients with Advanced HIV Disease (ACTG 050)
Alpha Interferon and Interleukin-2
AZT, Alpha Interferon, and GM-CSF
AZT in Asymptomatic HIV Infected Individuals (ACTG 019)
AZT in Hemophiliacs (ACTG 036)
AZT & GM-CSF
AZT and Interleukin-2
Betaseron (Beta Interferon) and Reduced Dose AZT in AIDS and Advanced
ARC patients
Pneumocystis carinii Pneumonia (PCP) protocols
Dapsone or Dapsone/Pyrimethamine for PCP Prophylaxis
Trimetrexate with Leucovorin Rescue for AIDS Patients with PCP and
Serious Intolerance to Approved Therapies (ATEU 039)
CMV Retinitis protocols
Foscarnet for CMV Retinitis
Toxoplasmosis protocols
Pyrimethamine and Dapsone for Toxoplasmosis
Miscellaneous protocols
HIV & Heart Disease Study
Previously covered protocols
Anti-retroviral protocols
Pneumocystis carinii Pneumonia protocols
Miscellaneous protocols
Other protocols
Anti-retroviral protocols
Pneumocystis carinii Pneumonia protocols
Miscellaneous protocols
***************************************************************************
ANTI-RETROVIRAL PROTOCOLS
----------------------------------
ALTERNATING AND INTERMITTENT DOSES OF 2',3'-DIDEOXYCYTIDINE (ddC) AND AZT IN
PATIENTS WITH ADVANCED HIV DISEASE (ACTG 050)
DESCRIPTION: This study will examine the tolerance for alternating and
intermittent regimens of zidovudine (also known as AZT) and ddC in persons
who have demonstrated true hematologic (blood system) intolerance to reduced
doses of AZT.
REQUIREMENTS: Participants must have: HIV infection confirmed by ELISA;
documented history of four or more weeks of AZT treatment (hemoglobin must
have been at least 9.5 mg/dl and granulocyte count must have been at least
1000 at the beginning of the treatment); documented history of hematologic
toxicity due to reduced dose AZT with recovery from that toxicity (recovery
from toxicity must be observable by the following lab results: an absolute
granulocyte count of more than 1000 cells/mm^3 and a hemoglobin of more than
9.5 with no transfusions given during the preceding four weeks); no
significant bilateral symptoms of peripheral neuropathy; either mild or no
bilateral signs of peripheral neuropathy (candidates with stable unilateral
neurologic deficit will not be excluded); the ability to care for most
personal needs requiring at most occasional assistance; attained at least 13
years of age (those between 13 and 18 must have written consent by parent or
legal guardian); no AZT administration within 14 days of entering the study;
and, if a woman of child-bearing potential, have a negative pregnancy test
with 30 days of entry in the study and use an effective method of birth
control during the study.
Participants must have laboratory values within certain limits: platelet
count of greater than 75,000/mm^3; calculated creatinine clearance of
greater than 50 ml/min/1.73m^2; and transaminase less than five times the
upper limit of normal.
Patients will be excluded from the study if they: have an active AIDS-
defining opportunistic infection; are receiving chronic anti-infective
therapy (other than inhaled aerosolized pentamidine as a preventive for
Pneumocystis Carinii pneumonia); have known mycobacteremia; have symptomatic
visceral Kaposi's sarcoma (KS), progression of KS within one month prior to
entry in the study or with neoplasms other than KS, basal cell carcinoma of
the skin or in-situ carcinoma of the cervix; demonstrate significant
malabsorption (a condition in which the body does not properly absorb
nutrients or drugs); are active substance (including alcohol) abusers; have
received any antiretrovirals except AZT within 30 days prior to entry (this
does not apply to AL-721, although its use is discouraged); are breast
feeding; have diabetes or are taking neurotoxic drugs.
ADMINISTRATION: Ninety-six patients who have recovered from dose-limiting
AZT toxicity (reaction) will be studied. Additional patients will be
enrolled to replace those who drop out of the study before it is finished.
All the AZT and ddC doses will be taken by mouth. The patients will be
randomly divided into six different treatment regimens.
A description of the six different groups follows:
1. Weekly Alternating. AZT is administered at 200 mg every four hours for
one week, after which AZT is stopped and ddC administration begins at 0.01
mg/kg (about 50 to 100 mg per patient depending on their weight) every four
hours for one week. After a week of the ddC regimen, AZT is again
administered for a week, then ddC again. There will be 24 consecutive
cycles, or 48 weeks, of therapy administered.
2. Weekly Alternating (higher dose of ddC). AZT is administered at 200 mg
every four hours for one week, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one week. After a
week of the ddC regimen, AZT is again administered for a week, then ddC
again. There will be 24 consecutive cycles, or 48 weeks, of therapy
administered.
3. Monthly Alternating. AZT is administered at 200 mg every four hours
for one week, after which AZT is stopped and ddC administration begins at
0.01 mg/kg every four hours for one week. After a week of the ddC regimen,
AZT is again administered for a week, then ddC again. A total of six
consecutive cycles, or 48 weeks, of therapy is administered.
4. Monthly Alternating (higher dose of ddC). AZT is administered at 200
mg every four hours for one week, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one week. After a
week of the ddC regimen, AZT is again administered for a week, then ddC
again. A total of six consecutive cycles, or 48 weeks, of therapy is
administered.
5. Weekly Intermittent (AZT only). AZT is administered at 200 mg every
four hours for one week, after which AZT is stopped and no drug is given for
one week. After a week with no drug given, AZT is again administered for a
week after which it is again stopped for one week. A total of 24
consecutive cycles, or 48 weeks, occur during the study. No ddC is given to
this group of the study.
6. Weekly Intermittent (ddC only). ddC is administered at 0.03 mg/kg
every four hours for one week, after which ddC is stopped and no drug is
given for one week. After a week with no drug given, ddC is again
administered for a week after which it is again stopped for one week. A
total of 24 consecutive cycles, or 48 weeks, occur during the study. No AZT
is given to this group of the study.
TERM: 48 weeks of treatment with four additional weeks of follow-up.
METHODOLOGY: Both AZT and ddC are potent inhibitors of HIV. (They are
Chain Terminators; see "A Layman's Guide to HIV" in the December, 1988
issue.) Both these drugs place the patient at risk for serious, but
different, side effects. Researchers hope to demonstrate through this study
that alternating the use of the two drugs will reduce the side effects while
maintaining the positive aspects of HIV inhibition.
CONTROLS: None
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Marybeth Goldin, George Washington University, (202) 994-2417
----------------------------------
ALPHA INTERFERON AND INTERLEUKIN-2
DESCRIPTION: An evaluation of the toxicity and effectiveness of the
combination of alpha interferon and interleukin-2 in the treatment of
patients with HIV infection.
REQUIREMENTS: Participants must: have evidence of HIV demonstrated by
ELISA and Western Blot or a positive culture for HIV; have a T4 cell count
of greater than or equal to 200/mm^3; be between the ages of 18 and 60; and
not have been exposed to chemotherapy, corticosteroid therapy or
experimental therapy for six weeks prior to entry. A negative pregnancy
test is required for women of child-bearing potential. All participants
must have a primary physician involved and available to communicate with NIH
staff during the study.
TERM: As an outpatient during the time it takes to gradually increase alpha
interferon doses to a maximum level, and hold the dose at maximum for two
weeks. As an inpatient, an additional 21 days of IL-2 infusion, with
outpatient follow-up visits for the next two months.
ADMINISTRATION: Alpha interferon is self-administered by the patient by
daily injection under the skin (much the same as the method used by
diabetics). Interleukin-2 is administered by injection into the vein
continuously for 21 days. There are weekly and bimonthly blood drawings and
clinic visits during the term of the study.
METHODOLOGY: Both alpha interferon and interleukin-2 are well-tolerated as
individual drugs in HIV-infected persons. Researchers are trying to
determine whether the use of both drugs simultaneously will result in
beneficial effects not seen in either when taken as single agents.
NOTES: Potential side effects of alpha interferon include flu-like
symptoms, a decrease in white cells, mental changes, gastrointestinal
disturbances, TEMPORARY hair loss, minor liver problems, and congestive
cardiomyopathy. Interleukin-2 has also been associated with some side
effects such as proteinuria, mild prolongation of PTT, fever, hepatitis,
rigors, increased incidence of bacterial infection, and eosinophilia. All
these effects improved or disappeared after discontinuation of the drugs.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------
AZT, ALPHA INTERFERON, AND GM-CSF
DESCRIPTION: This study is designed to evaluate the safety and
effectiveness of giving recombinant granulocyte-macrophage colony
stimulating factor (GM-CSF) in combination with AZT and alpha interferon in
patients with HIV infection.
REQUIREMENTS: Participants must: be over age 18; have a CD4 count of 200
to 500 per cubic millimeter; be positive for HIV on both the ELISA and the
Western Blot; have good veins; and be under the care of a physician with
whom the researchers can communicate while they are on the study. People
with active opportunistic infections are excluded.
TERM: Sixteen weeks after the dosages have stabilized, all of which is
outpatient.
ADMINISTRATION: Newly enrolled patients will be divided into two groups.
One group will receive 100 mg of AZT orally every four hours for four weeks,
and then will begin on interferon with 10 million units/day by injection
under the skin with the dose escalating by five million units/day every two
weeks. When the granulocyte count falls below 1000/mm^3, GM-CSF will be
started at a dose of 1 microgram (ug) per kilogram of body weight per day
(ug/kg/day), by injection under the skin. The GM-CSF dose will be escalated
to maintain the granulocyte count over 1500/mm^3. Once the patient's
granulocyte count is stable on AZT, interferon, and GM-CSF, the patient will
be treated for 16 weeks. The second group is identical to the first, except
their starting AZT dose will be 200 mg every four hours. Enrollment will be
done sequentially--the first 10 patients will be in the first group, and the
second 10 will be in the second group.
NIH patients who have previously been on combination AZT/interferon therapy
will comprise a third group. Patients in this group will begin on AZT and
interferon at the doses at which they became granulocytopenic (low counts of
granulocytes) in the past, with GM-CSF at one ug/kg/day starting at the same
time. Doses of AZT, interferon, and GM-CSF will be escalated, as tolerated,
in an attempt to bring the patients up to an optimal dosing level of AZT 200
mg every four hours and interferon 10 million units per day. The treatment
period for the third group, once the patient's granulocyte count is
stabilized above 1500/mm^3, will also be 16 weeks.
METHODOLOGY: While studies in the laboratory and in humans have shown that
AZT and alpha interferon given together can inhibit HIV, up to 50% of
patients taking this combination of drugs develop granulocytopenia, a
potentially serious decrease in a particular infection-fighting white blood
cell known as the granulocyte. Granulocyte-macrophage colony stimulating
factor is a bone marrow growth factor that stimulates production of several
types of cells found in blood, including the granulocyte.
NOTES: Potential side effects of AZT include nausea, headaches, and anemia
that may require blood transfusion. Interferon can cause flu-like symptoms
(fevers, fatigue, muscle aches, decrease in appetite), a decrease in white
blood cell count, and mental changes, including depression, memory loss, and
difficulty concentrating. The combination of AZT and interferon has been
known to cause a decrease in granulocytes and depression of liver function.
GM-CSF can cause fever, bone pain, and flu-like symptoms in some patients.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases, Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892, (301) 496-7196
----------------------------------
AZT IN ASYMPTOMATIC HIV INFECTED INDIVIDUALS (ACTG 019)
DESCRIPTION: This study is designed to show whether AIDS and ARC can be
prevented or delayed in people infected with HIV who are still healthy. A
comparison will be made between the dose of AZT (also known as zidovudine
and Retrovir) useful in AIDS and severe ARC with a lower dose to see if the
lowered dose is still effective. This is a double-blind placebo-controlled
study, which means that 67 percent of the patients will get some dosage of
AZT and 33 percent will get no treatment at all during the course of the
study. Neither the patient nor the researchers will know who is in what
group until the study is finished.
REQUIREMENTS: To be eligible for this study, all participants must be at
least 18 years old; have HIV infection as determined by ELISA and confirmed
by Western Blot; not meet the CDC (Centers for Disease Control) definition
for either AIDS or ARC. Participants must have laboratory results within
certain limits: hemoglobin greater than 13 gm/dl (males) or 12 gm/dl
(females); absolute neutrophil count of at least 1500 cells/mm^3; platelet
count of at least 100,000 cells/mm^3; normal serum creatinine; and have SGPT
and SGOT less than 1.5 times the upper limits of normal. Women of child-
bearing potential must practice abstinence or birth control; have a negative
pregnancy test within 30 days of entry into the study; and must not be
breast feeding.
Patients will be excluded from the study who: have suffered unintentional
weight loss greater than 10 pounds or 10 percent of body weight within two
years prior to entry to the study; have had unexplained temperature above
38oC (about 100.5oF) on more than five consecutive days or on more than ten
days during any 30 day period within the two years prior to the study, or
have a current temperature higher than 37.8oC (100oF); have had drenching
night sweats within the past two years; have had unexplained diarrhea (three
or more liquid stools per day persisting for more than seven days) within
two years prior to the study or have current active diarrhea; have had oral
candida (thrush) within two years of the study; have had oral hairy
leukoplakia (white spots or patches on the tongue or cheek) at any time
prior to the study; have had herpes zoster infection (shingles) within two
years of the study; are active alcohol or drug abusers; have received
antiretroviral drugs or immunomodulators within 60 days prior to the study;
have been treated with corticosteroids within 120 days of the study; have a
history of malignancy (tumors) other than cutaneous basal cell carcinoma (a
non-malignant skin cancer) or cervical carcinoma in-situ; have significant
underlying illnesses which would impair participation in a three year study;
have hemophilia; have some degree of neurological impairment; or have had a
blood transfusion within the three months prior to entry in the study.
TERM: Continuous, possibly until 1991.
ADMINISTRATION: All treatment doses will be given by capsules taken by
mouth. Patients will be divided into three treatment groups. The first
group will receive a relatively high dose of AZT five times daily. The
second group will receive a lower dose of AZT along with a placebo five
times daily. The third group will receive only a placebo five times daily.
No patient will know which group she/he is in. Participants will be
required to visit the clinic every two weeks during the first 16 weeks of
the study, and monthly thereafter.
METHODOLOGY: Zidovudine acts as an inhibitor to the copying mechanism of
HIV. (See "A Layman's Guide to HIV" in the December, 1988 issue.) Large
doses of this medication have often resulted in adverse side effects in
patients with AIDS and severe ARC. Researchers are, through this study,
attempting to find out if doses lower than those customarily given to AIDS
and ARC patients might delay or arrest the development of these stages of
the disease in healthy HIV seropositive individuals without the negative
side effects.
NOTES: Possible side effects from AZT include: headache, muscle aches,
nausea, vomiting, anemia, lowering of the white blood cell count, and
lowering of the platelet count.
CONTROLS: This is a randomized double-blind placebo-controlled study. This
means that during the course of the study neither the patient nor the
researchers will know who is receiving Zidovudine or the placebo.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Jane Courtless, R.N., George Washington University, (202) 994-2417
----------------------------------
AZT IN HEMOPHILIACS (ACTG 036)
DESCRIPTION: This is a double-blind placebo-controlled study to determine
whether AZT (also known as zidovudine or Retrovir) will delay or alter the
progression of disease in HIV infected hemophiliacs.
REQUIREMENTS: Participants must: have HIV infection confirmed by Western
Blot; be at least 12 years old; and have been diagnosed with hemophilia, Von
Willebrand's Disease, or other coagulation-deficient disorders.
Participants must have laboratory results within certain limits:
granulocyte count of at least 1000 cells/mm^3; platelet count of a least
75,000/mm^3; hematocrit greater than 30 percent; creatinine less than or
equal to 1.5 times normal or clearance of at least 50 ml/min; and
transaminases less than or equal to five times the upper limit of normal.
Participants must also have a Karnofsky performance status of 90 (able to
carry on normal activity; minor signs or symptoms or disease), although if
this measure in impaired by hemophilia complications, a status as low as 60
will be accepted (requires occasional assistance but is able to care for
most of his/her needs).
Patients will be excluded from the study if there is a history of AIDS
defining infection or malignancy or an unexplained temperature higher than
38oC (about 100.5oF) for more than five consecutive days or on more than 10
days in any 30-day period in the two years before entering the study.
Additional exclusions are: unexplained severe diarrhea; unintentional
weight loss of more than 10 percent of body weight in the past two years;
oral hairy leukoplakia (white spots or patches on the tongue or cheek); a
history of oral candidiasis not related to antibiotics; or herpes zoster
infection within the past two years. People will also be excluded if: they
have taken antiretroviral agents (like AZT) within the last eight weeks or
immunomodulating drugs (like steroids); they have taken other experimental
therapy within three months; or if they require therapy with isoniazid or
rifampin. All participants will be required to practice effective
contraception, and pregnancy is a basis for exclusion from the study.
TERM: Up to three years
ADMINISTRATION: Participants will take orally three 100 mg capsules every
four hours for five doses per day. Half of these persons will be receiving
AZT, the other half will be receiving a harmless placebo.
METHODOLOGY: AZT acts on HIV to inhibit its replication (reproduction or
copy of itself). It is a chain terminator (see explanation in A Layman's
Guide to HIV in the December, 1988 issue).
CONTROLS: This is a double-blind, placebo-controlled study, which means 50%
of the patients will get AZT, and 50% will get none. Neither the patient
nor the researchers will know which is which during the course of the study.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Naomi Israel, George Washington University, (202) 994-4200
----------------------------------
AZT & GM-CSF
DESCRIPTION: Phase I study of AZT (Azidothymidine) combined with GM-CSF
(Granulocyte/Macrophage-Colony Stimulating Factor) in patients with AIDS or
symptomatic HIV infection.
REQUIREMENTS: All participants must be at least 18 years old and have T4
cell counts of less than 200. Participants must have either never taken
AZT, or have taken at least 600mg a day, and discontinued because of
toxicity to the patient's white blood cells. Participants who were on AZT
must be off it for at least four weeks prior to the study. All participants
must have a white blood cell count of less than 4,500 per cubic millimeter,
hemoglobin of greater than nine grams per deciliter, and neutrophil (which
are mature white blood cells) counts of less than 1,500 per cubic millimeter
if the participant has never been on AZT. All participants must have
greater than 75,000 platelets per cubic millimeter and no transfusions
within the past month. People with active opportunistic infections are
excluded from the study. No other cytotoxic or antiretrovirals may be taken
while participants are in the protocol, although prophalaxis for PCP with
either Fanzidar, Bactrim, or aerosolized Pentamidine is permitted. Women
of child-bearing potential must have a negative pregnancy test prior to the
start of the study, and be willing to use birth control measures during and
for two months after the study.
TERM: Six months, with the possibility of an extension if the patient
responds favorably to the treatment. All treatment is on an outpatient
basis from the NIH Clinical Center.
ADMINISTRATION: The AZT is given orally every four hours; the GM-CSF is
given three times a day by a self-administered injection just under the skin
(similar to the way insulin is self-injected by diabetics).
METHODOLOGY: AZT, while effective at suppressing the reproduction of HIV,
has an unfortunate side effect of supressing the production of granulocytes
and macrophages, which are types of white blood cells, within the bone
marrow. GM-CSF stimulates the production of granulocytes and macrophages,
so it is hoped that by taking GM-CSF in combination with AZT, AZT's toxic
side effects can be reduced or eliminated, or that a larger dose of AZT with
tolerable side effects will be possible.
NOTES: If the patient's white cell counts fall while he/she is in the
study, the dosage of GM-CSF will be increased (two increases only) to try to
counter the toxicity problems.
CONTROLS: None (In a Phase I study, all patients receive the actual
drugs.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. James Pluda, Building 10, Room 13N248, National institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop) (301) 496-8398
----------------------------------
AZT AND INTERLEUKIN-2
DESCRIPTION: The study will evaluate the effectiveness and toxicity of the
combination of AZT (also known as zidovudine and Retrovir) and Interleukin-2
(IL-2) in the treatment of persons with HIV infection.
REQUIREMENTS: To be eligible to participate in the study, a person must
have HIV diagnosed by ELISA and Western Blot or a positive culture. The
person must not have had any of the opportunistic infections associated with
AIDS and must have over 200 T4 cells per cubic millimeter. If the person is
receiving AZT, he/she must be able to tolerate 200 mg every four hours.
TERM: Seventeen weeks (with possible extension of therapy if significant
improvement occurs)
ADMINISTRATION: AZT alone will be given for six weeks (orally). Following
that, AZT and IL-2 will be administered for three weeks. The IL-2 will be
administered IV continuously for three weeks and this part of the study will
be done on an inpatient basis. In addition there will be weekly or biweekly
blood drawing for the duration of the study.
METHODOLOGY: Studies have demonstrated that AZT can decrease the frequency
of opportunistic infections, but it sometimes results in bone marrow
suppression. IL-2 is a drug which stimulates the immune system.
Researchers are trying to determine whether the IL-2 might reduce the side
effects of AZT, thus allowing more patients to take full doses of AZT.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------
BETASERON (BETA INTERFERON) AND REDUCED DOSE AZT IN AIDS AND ADVANCED ARC
PATIENTS
DESCRIPTION: Comparative study of high dose Betaseron, low dose Betaseron,
or placebo in combination with reduced dose AZT.
REQUIREMENTS: Patients must have: laboratory evidence of HIV infection;
either AIDS by CDC criteria or documentation of an absolute T4 count less
than 200; a reaction to AZT that requires dose reduction of AZT to 500-600
mg of AZT daily and the ability to tolerate this reduced dose; Karnofsky
status of 60 or greater (be able to take care of daily needs requiring only
occasional assistance); acceptable renal (kidney) function; acceptable
hepatic (liver) function; attained at least age 18; be available for follow-
up; and be willing to continue on reduced dose AZT at own expense.
Participants must have laboratory results within certain limits:
granulocyte count currently greater than 1000/mm^3; hemoglobin greater than
8.5 mg/dl; and platelet count greater than 50,000/mm^3. People will be
excluded if they have: ineffectively controlled opportunistic infections;
Kaposi's sarcoma requiring systemic chemotherapy; cytotoxic chemotherapy
within 30 days of the first Betaseron dose; proteinuria of 2+ or greater;
concurrent therapy with anti-virals other than AZT or Betaseron; chronic
concurrent therapy with acyclovir; prior therapy with interferon; HIV
encephalopathy (dementia); HIV wasting syndrome; pregnancy or lactation
(women with childbearing potential must take adequate precautions to prevent
pregnancy during treatment); active drug or alcohol abuse; New York heart
classification III or IV; uncontrolled angina pectoris (severe pain about
the heart, usually travelling down the left arm); or evidence of clinically
significant multifocal uncontrolled cardiac dysrhythmias.
TERM: Indefinite. The study will continue until the superiority of the
treatment is clearly demonstrated or disproved.
ADMINISTRATION: All patients continue on reduced dose AZT. Each patient is
assigned to one of three treatment groups--high dose Betaseron, low dose
Betaseron, or placebo. The patient administers daily injections of the
study drug into the skin (in the same way that diabetics inject themselves).
The patient must visit the test site for lab and physical evaluations once a
week for a month, biweekly for two months, and monthly thereafter.
METHODOLOGY: Many patients on AZT develop side effects which involve the
blood and must, therefore, be put on a reduced dose of AZT. In the
laboratory, Betaseron (a recombinant form of interferon Beta) has been shown
to enhance the action of AZT in blocking the ability of the HIV to make
copies of itself, to kill lymphocytes, and to spread between lymphocytes.
In clinical studies, patients who have taken Betaseron have shown evidence
of suppression of the HIV copying mechanism and a low incidence of
opportunistic infections. Although there may be side effects from
Betaseron, they are seldom related to the blood. As a result, researchers
believe that a level of AZT which is not toxic to the patient might be
combined with Betaseron to get positive results similar to a higher AZT dose
without the negative side effects of AZT on the blood.
NOTES: Possible side effects of Betaseron include mild flu-like symptoms
and redness at the injection site. These effects generally decrease and
disappear with continuing treatment. Sometimes a mild depression in blood
cell counts occurs.
CONTROLS: Two out of three patients will be given Betaseron, with the third
patient on a placebo. Although the study is placebo controlled, it should
be noted that all patients will be maintained on low doses of AZT, thus
ensuring that all patients will be receiving at least some anti-viral
therapy.
ORGANIZATION: George Washington University Hospital
CONTACT: Grace Gianturco, (202) 994-2417
***************************************************************************
PNEUMOCYSTIS CARINII PNEUMONIA (PCP) PROTOCOLS
----------------------------------
DAPSONE OR DAPSONE/PYRIMETHAMINE FOR PCP PROPHYLAXIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity and
efficacy of weekly dapsone or dapsone/pyrimethamine in HIV-infected persons
with prior history of PCP or who have less than 250/mm^3 CD4 cells.
REQUIREMENTS: Participants must be: 18 years of age or older; HIV
positive; and able to provide informed consent. Participants must have
either a history of documented PCP that has been successfully treated or a
CD4 count of less than 250/mm^3. Participants must be at least two weeks
from other anti-PCP prophylaxis.
TERM: One year if beneficial, or stopped if the participant develops PCP or
significant toxicity while on therapy
ADMINISTRATION: This is an outpatient study comprised of two phases. The
initial phase will consist of open dose escalation with the first five
participants receiving dapsone 100 mg orally once a week. Dose escalation
will continue in increments of 100 mg every five participants until dose-
limiting toxicity is reached in 20% of patients at a given dose. After
establishment of a tolerated dose of dapsone, pyrimethamine 25 mg will be
added. After the dose escalating phase is completed, all subsequently
entered participants will be randomized to receive either dapsone or
dapsone/pyrimethamine. Participants will be seen in the outpatient clinic
weekly for four weeks, then every two weeks for lab work and every six weeks
for nursing visits for a period of one year.
METHODOLOGY: A study of PCP in a rat model suggests that intermittent
administration of dapsone, which is a sulfone, could prevent development of
PCP. Efficacy of dapsone appears to be enhanced by a dihydrofolate
reductase inhibitor, trimethoprim, therefore it is possible that such agents
used in combination could result in improved prevention against PCP.
Pyrimethamine is a more potent agent against PCP than trimethoprim and is
effective for a longer period in the body. Combination dapsone and
pyrimethamine therapy has the advantage of being potentially well-tolerated,
easily administered, and inexpensive.
NOTES: Possible side effects include anemia, methemoglobinemia (a condition
in which the hemoglobin has been changed by a toxic substance), decreased
white blood cells, hepatitis, rash, nausea, and fatigue.
CONTROLS: None
ORGANIZATIONS: Georgetown University Hospital: Center for HIV Disease;
National Institutes of Health: National Institute of Allergy and Infectious
Diseases (NIAID)/National Cancer Institute (NCI)/Clinical Center
CONTACTS: Georgetown University Hospital (Center for HIV Disease): Dr.
James Lavelle, Georgetown University Hospital, 3800 Reservoir Road, N.W.,
Washington, DC 20007 (202) 687-8826
National Institutes of Health: Debbie Ogata-Arakaki, Building 10, Room
10D48, National Institutes of Health, Bethesda, MD 20892 (301) 496-9565
----------------------------------
TRIMETREXATE WITH LEUCOVORIN RESCUE FOR AIDS PATIENTS WITH PCP AND SERIOUS
INTOLERANCE TO APPROVED THERAPIES (ATEU 039)
DESCRIPTION: To determine the safety and efficacy of trimetrexate with
leucovorin rescue in AIDS patients with PCP who have no therapeutic
alternatives because they have demonstrated severe or life-threatening
intolerance to both pentamidine and trimethoprim/sulfamethoxazole (T/S, also
known as Bactrim).
REQUIREMENTS: Participants must: have attained at least age 12 (those
under 18 must have consent by parent or legal guardian); be HIV positive by
ELISA, HIV culture, or p24 antingemia or have a history of male homosexual
or bisexual behavior, or of intravenous drug use, or of being the recipient
of HIV-infected blood products, or of being the sexual partner of persons in
these groups; have an unequivocal diagnosis of pneumocystis carinii
pneumonia (PCP) confirmed by test; have demonstrated intolerance to both
pentamidine and trimethoprim/sulfamethoxazole (T/S, or Bactrim); and women
in the study must have a negative pregnancy test and agree to use barrier
contraception throughout the study. Participants must have laboratory
results within certain limits: serum creatinine less than or equal to 2.5
mg/dl; serum bilirubin less than or equal to three times the upper limit of
normal; serum transaminases (SGOT, SGPT) less than or equal to five times
the upper limit of normal; absolute neutrophil count greater than or equal
to 1000/mm^3; and platelet count greater than or equal to 50,000/mm^3.
People who are currently involved in other investigational therapies, or who
are breast feeding are excluded.
TERM: 24 days, all of which are inpatient.
ADMINISTRATION: Trimetrexate will be administered by vein once a day and
leucovorin by vein every six hours. The trimetrexate therapy will last for
21 days, the leucovorin therapy will last for the entire 24 days of study.
Blood tests will be taken several times a week to check for toxicity to the
medications being administered.
METHODOLOGY: Trimetrexate is a drug used to kill the organism which causes
PCP. Because trimetrexate is a very potent drug which can have negative
side effects, in this study it is given in conjunction with leucovorin,
which is a vitamin that reduces these side effects. Because PCP is a deadly
disease, those who are unable to take the two drugs which are currently
available to fight it are at great risk. Researchers hope that this
investigational treatment will provide an alternative therapy for those
patients who currently have none.
NOTES: Patients currently on AZT therapy will have to discontinue that
therapy during the 24-day duration of the study. AZT can be resumed
immediately after completion of the study.
CONTROLS: None
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH
CONTACT: Jane Courtless, R.N., George Washington University, (202) 994-2417
***************************************************************************
CMV RETINITIS PROTOCOLS
----------------------------------
FOSCARNET FOR CMV RETINITIS
DESCRIPTION: Study of the safety and effectiveness of foscarnet in AIDS
patients who have CMV retinitis.
REQUIREMENTS: This study is for people ages 18 to 60 with AIDS and a
positive HIV test who have CMV retinitis which is not immediately sight-
threatening. One or both eyes may be affected by the retinitis.
Participants must designate someone with a Durable Power of Attorney, and
must also satisfy certain laboratory conditions (serum creatinine less than
or equal to 2.0 mg/dl; neutrophil counts of greater than 1000/mm^3;
hemoglobin of greater than or equal to 8 g/dl; and platelets of greater than
25,000/mm^3). The following people are excluded: those who have been
treated with ganciclovir or foscarnet for CMV retinitis in the past; those
who are currently taking acyclovir orally or intravenously; those who have a
history of intolerance to AZT; those with corneal, lens, or vitreous
opacification which precludes fundus examination, or other retinal diseases;
and people taking other investigational drugs. Women must have a negative
pregnancy test within 14 days of the start of the study, and agree to
practice contraception for the duration of the study plus three months
afterwards.
TERM: Three weeks of inpatient treatment at the NIH Clinical Center for
those receiving foscarnet, then outpatient treatment until significant
progression of the CMV retinitis is observed. Patients who complete the
study can continue receiving foscarnet from the manufacturer at no charge
until it becomes a marketed drug.
ADMINISTRATION: Patients must undergo a physical examination including
blood tests, a chest x-ray, electrocardiogram, and tests to determine the
severity of the CMV retinitis. Patients will be randomly divided into three
groups. The first group will receive foscarnet intravenously three times a
day as inpatients at NIH for three weeks, and then once a day as
outpatients. The second group will receive the same treatment as the first
group, plus oral AZT. A third group will receive only AZT. Patients in all
groups will also receive aerosolized pentamidine to lower the risk of
Pneumocystis carinii pneumonia. Patients receiving foscarnet will have a
Hickman catheter inserted. This device is a plastic tube inserted in a
large central vein through which the drug is administered. This eliminates
the need to administer the drug into a peripheral vein each time. The tube
is placed during a simple surgical procedure performed under general
anesthesia.
Patients will be examined weekly to check for progression of the CMV
retinitis. If significant disease progression occurs in the patients
receiving only AZT, foscarnet will be made available to them.
Frequent blood testing is also required, up to 450 ml in a six-week period.
Urine tests will be taken once a week during the first three weeks, then
once every two weeks for the rest of the study.
METHODOLOGY: Foscarnet has been proven to inhibit viral activity in human
herpes viruses by interfering with the ability of the viruses to reproduce
themselves without significantly interfering with the ability of the rest of
the body's cells to reproduce. Foscarnet has been used as a treatment for
CMV in Europe, Canada, and the United States. Foscarnet also does not
appear to have the toxic effects on bone marrow that AZT does, thus giving
hope that people with CMV retinitis may have an effective treatment for this
disease without having to stop taking AZT. Ganciclovir (also known as
DHPG), the other treatment being explored for CMV retinitis, cannot be taken
at the same time as AZT. Foscarnet also has some action against HIV.
NOTES: Possible side effects of foscarnet include decreased kidney
function, confusion, inflammation of the veins, anemia, headache, fatigue,
and seizures. The Hickman catheter used for injection of the Foscarnet can
also become infected. AZT may cause decreased white blood cell counts,
making the patient more susceptible to infection, or anemia. Aerosolized
pentamidine may cause constriction of the bronchial airways.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Eye Institute/National
Institute for Allergy and Infectious Diseases
CONTACT: Dr. Judith Rubin, (301) 496-1243
***************************************************************************
TOXOPLASMOSIS PROTOCOLS
----------------------------------
PYRIMETHAMINE AND DAPSONE FOR TOXOPLASMOSIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance
and effectiveness of combination therapy with dapsone and pyrimethamine for
the treatment of central nervous system toxoplasmosis in persons with AIDS
who are resistant to or intolerant of conventional therapy.
REQUIREMENTS: Participants must: have AIDS as defined by the Centers for
Disease Control; be at least 18 years of age; be able to sign an informed
consent; and be willing to sign a durable power of attorney. Participants
must have cerebral toxoplasmosis and either have been intolerant of or
failed conventional therapy (pyrimethamine and sulfadiazine).
TERM: Life-long if therapy is beneficial. Study will be stopped if the
participant deteriorates at 14 days of therapy or fails to improve at 21
days of therapy.
ADMINISTRATION: Participants will receive oral daily doses of pyrimethamine
25 mg, dapsone 100 mg, and leucovorin 10 mg. Adjustments of pyrimethamine
and dapsone will be made if the participant fails to respond. All
participants will be admitted to the NIH Clinical Center for induction of
therapy. After seven inpatient days, participants medically stable and
reliable will be discharged to continue therapy as outpatients.
Participants will be seen in the NIH outpatient clinic weekly for the first
three weeks, and every two weeks thereafter.
METHODOLOGY: Toxoplasmosis is a life-threatening parasitic infection caused
by a protozoa, toxoplasma gondii. Pyrimethamine, a dihydrofolate reductase
inhibitor and dapsone, a sulfone agent, are known to block folic acid
metabolism, an important pathway in both humans and toxoplasma organisms.
Leucovorin, mentioned above, allows the body's cells to bypass the blockade
without affecting the anti-protozoan activity. In combination, these drugs
have the potential to be at least as effective as the conventional regimen,
pyrimethamine and sulfadiazine, but less toxic, for treatment of
toxoplasmosis.
NOTES: Possible side effects include a decrease in white blood cell count
or platelet count, anemia, methemoglobinemia, hepatitis, kidney problems,
rash, nausea, and vomiting.
CONTROLS: None
ORGANIZATION: National Institutes of Health: National Institute of Allergy
and Infectious Diseases (NIAID)/National Cancer Institute (NCI)/Clinical
Center
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892, (301) 496-9565
***************************************************************************
MISCELLANEOUS PROTOCOLS
----------------------------------
HIV & HEART DISEASE STUDY
DESCRIPTION: Long-term study of heart disease in people who are infected
with HIV.
REQUIREMENTS: Participants must be HIV positive.
TERM: The study is expected to run until June, 1993.
ADMINISTRATION: Participants will go to the study center every four months,
and will undergo three non-invasive tests of their hearts: an EKG
(electrocardiogram), an echocardiogram, and a Signal Averaged EKG (a more
sensitive, computer-processed version of the EKG). Blood will also be drawn
for analysis. Study hours are on Tuesdays, from 8:00 a.m. to 1:00 p.m. If
abnormalities are detected, participants will be asked to return every two
months.
METHODOLOGY: The EKG and other tests help analyze the condition of your
heart. The blood work checks for antibodies to heart antigens. The two
primary heart diseases being watched for are cardiomyopathy (enlargement of
the heart), and pericardial effusions (which are fluids in the sack around
the heart).
Seventy percent of AIDS patients showed cardiac problems at autopsy, many of
these problems might have been amenable to treatment with appropriate drugs.
Monitoring can help detect these types of problems early enough that they
can be treated. Many people who aren't HIV-positive but have a history of
heart disease in their family undergo this type of monitoring as a matter of
routine.
No actual treatment is performed during this study. If problems are
detected, participants are referred to their physician for treatment. Full
cooperation and access to medical records will be provided by the
researchers.
NOTES: Participants will have their results evaluated by and be seen by a
cardiologist every time they come in for testing. Confidentiality of
patient records is maintained. Copies of all testing records are sent on
request to either the participant or the participant's physician.
CONTROLS: Not applicable
ORGANIZATION: George Washington University Hospital, Division of Cardiology
CONTACT: Sara Adams, Room 2440 North, George Washington University
Hospital, 901 23rd Street, N.W., Washington, DC 20037, (202) 994-3909
***************************************************************************
PREVIOUSLY COVERED PROTOCOLS
Protocols covered in December 1988 issue of WHN:
--------------------------------------------------------------------------
ANTI-RETROVIRAL PROTOCOLS
AZT & ALPHA INTERFERON (AZT alone vs. AZT and Alpha Interferon vs. Alpha
Interferon alone, for people in the early stages of HIV infection) AZT
inteferes with replication of HIV. Alpha interferon interferes with the
final assembly process of HIV.
National Institutes of Health/National Institute of Allergy and Infectious
Diseases (NIAID), Victoria Davey, (301) 496-7196
AZT FOR VETERANS (double-blind, placebo-controlled study of patients with
ARC) AZT inteferes with replication of HIV.
Veterans Administration Hospital Medical Center, Mary Elena Seiler or Megan
Wholey, (202) 745-8694
AZT IN EARLY ARC (ATEU 016) AZT inteferes with replication of HIV.
George Washington University, Jane Courtless, (202) 994-2417
CHEMOTHERAPY AND AZIDOTHYMIDINE (AZT) WITH OR WITHOUT RADIOTHERAPY (ATEU
008) (treatment for high grade lymphoma in AIDS-risk group members) AZT
interferes with replication of HIV. Chemotherapy and radiotherapy are
standard treatments for cancer.
George Washington University, Jane Courtless, (202) 994-2417
CHEMOTHERAPY, RADIOTHERAPY AND AZT FOR AIDS-RELATED PRIMARY CENTRAL NERVOUS
SYSTEM (CNS) LYMPHOMA (ATEU 009) AZT interferes with replication of HIV.
Chemotherapy and radiotherapy are standard treatments for cancer.
George Washington University, Jane Courtless, (202) 994-2417
ddI (2',3'-DIDEOXYINOSINE) A chemical similar in action to AZT.
National Institutes of Health/National Cancer Institute, Dr. Robert
Yarchoan, (301) 496-0328
ORAL DEXTRAN SULFATE (ACTG 060) Dextran Sulfate appears to have some effect
on preventing the binding of HIV to blood cells.
George Washington University, Jane Courtless, (202) 994-2417
RECOMBINANT SOLUBLE CD4 A genetically engineered drug which mimics the
receptor for HIV and therefore competes for virus, binds it, and prevents
virus attachment to blood cells.
National Institutes of Health/National Cancer Institute, Dr. Robert
Yarchoan, (301) 496-0328
--------------------------------------------------------------------------
PNEUMOCYSTIS CARINII PNEUMONIA PROTOCOLS
AEROSOLIZED PENTAMIDINE FOR SINGLE EPISODE OF PCP Aerosolized pentamidine
helps prevent the recurrence of PCP.
Veterans Administration Hospital Medical Center, Mary Elena Seiler, (202)
745-8694
AEROSOLIZED PENTAMIDINE FOR MULTIPLE EPISODES OF PCP FOR VETERANS
Aerosolized pentamidine helps prevent the recurrence of PCP.
Veterans Administration Hospital Medical Center, Megan Wholey, (202) 745-
8694
--------------------------------------------------------------------------
MISCELLANEOUS PROTOCOLS
----------------------------------
AEROSOLIZED GAMMA-INTERFERON A Phase I study to determine drug toxicity and
effectiveness in stimulating anti-microorganism activities of lung
macrophages (white blood cells).
National Institutes of Health/National Heart, Lung, and Blood Institute,
Pulmonary Branch, (301) 496-2449
BLOOD DRAWING STUDY The blood will be used in research studies.
National Institutes of Health/National Heart, Lung, and Blood Institute,
Pulmonary Branch, (301) 496-2449
BRONCHOALVEOLAR LAVAGE STUDY Research study to determine what organisms
attack the lungs and how the lungs' defense mechanisms operate.
National Institutes of Health/National Heart, Lung, and Blood Institute,
Pulmonary Branch, (301) 496-2449
gp-160 (Trial vaccine against HIV) A genetically-engineered protein that is
part of the envelope for HIV. Hopefully, the body will develop antibodies
to gp-160 which will also be effective against HIV.
National Institutes of Health/National Institute of Allergy and Infectious
Diseases (NIAID), Margaret Easter, (301) 496-7196
--------------------------------------------------------------------------
OTHER PROTOCOLS
The following is a list of protocols, compiled by Dr. Basil Vareldzis,
Clinic Director of the Whitman-Walker Clinic, of other protocols available
in the Washington area. Future issues will carry more in-depth descriptions
of these protocols.
----------------------------------
ANTI-RETROVIRAL PROTOCOLS
ALTERNATING AND INTERMITTENT DOSES OF ddC AND AZT IN PATIENTS WITH AIDS AND
ARC (ACTG 047) Similar to ACTG050, but for AIDS and ARC patients.
George Washington University, Marybeth Goldin, (202) 994-2417
EFFECT OF AZT ON HIV ASSOCIATED NEUROLOGICAL AND/OR NEUROMUSCULAR
DYSFUNCTION
National Institutes of Health/National Institute of Mental Health, Valita
Fredland, (301) 496-2429
EFFICACY OF B12/FOLATE FOR PATIENTS ON AZT
Georgetown University, Dr. Mary Young, (202) 687-8672
NEUROPSYCHIATRIC CHANGES ACCOMPANYING ALPHA INTERFERON THERAPY IN TREATMENT
OF HIV VIREMIA
National Institutes of Health/National Institute of Mental Health, Dr. Mark
Dimitrack, (301) 496-6565
NEUROPSYCHIATRIC CHARACTERIZATION OF HIV ANTIBODY POSITIVE PERSONS ON AZT
Georgetown University, Pim Brouwers, (202) 687-4954
--------------------------------------------------------------------------
PNEUMOCYSTIS CARINII PNEUMONIA PROTOCOLS
AEROSOLIZED PENTAMIDINE: (single previous episode of PCP)
Georgetown University, Dr. Philip Pierce, (202) 687-8672
AEROSOLIZED PENTAMIDINE: (multiple episodes of PCP)
Georgetown University, Dr. Philip Pierce, (202) 687-8672
--------------------------------------------------------------------------
MISCELLANEOUS PROTOCOLS
BRAIN METABOLISM IN HIV DISEASE
National Institutes of Health/National Institute of Mental Health, Dr. Tom
Nordahl, (301) 496-4707
EVENT RELATED BRAIN POTENTIALS IN HIV DISEASE
National Institutes of Health/National Institute of Mental Health, Dr.
Christine Ollo, (301) 496-6565
MEASUREMENT OF EYE MOVEMENT IN HIV DISEASE
National Institutes of Health/National Institute of Mental Health, Dr.
Robert Litman, (301) 496-6295
NEUROPSYCHIATRIC MANIFESTATIONS OF HIV INFECTION
National Institutes of Health/National Institute of Mental Health, Dr.
Christine Ollo, (301) 496-6565
SALIVARY FUNCTION IN HIV INFECTED INDIVIDUALS
National Institutes of Health/National Institutes of Allergy and Infectious
Diseases, Dr. Yeh, (301) 496-1478
***************************************************************************
It is the intent of Washington HIV News to only list protocols which are
open to new patients. Some protocols may be on a temporary hold while the
inclusion criteria are being revised. Others, which had a projected start
date a few weeks after the publication date for this issue, were not
included because they were not actually underway and accepting patients.
Therefore, people with specific needs or interests are encouraged to call
around if they do not see a protocol listed for their needs, because
protocols may have either started or come off of hold after press time.
***************************************************************************
Copyright (C) 1988,1989 by Washington HIV News, all rights reserved.
Permission is granted for non-commercial use only.
--
J. Philip Miller, Professor, Division of Biostatistics, Box 8067
Washington University Medical School, St. Louis MO 63110
phil@wubios.WUstl.edu - Internet (314) 362-3617 phil@wubios.wustl - bitnet
uunet!wucs1!wubios!phil - UUCP C90562JM@WUVMD - alternate bitnet