rock@uunet.UU.NET (02/25/90)
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TREATMENT - Table of Contents January 1990 - Vol 1, No 4
Anti-retroviral protocols
AZT and Acyclovir
AZT & Acyclovir, ddI, and ddC combination study
ddC (2',3'-dideoxycytidine) vs. AZT (Retrovir or Zidovudine) in
patients with advanced ARC or AIDS
ddI vs. AZT for people with AIDS or Advanced ARC with no or short-term
prior AZT (ACTG 116)
ddI vs. AZT for people with AIDS or Advanced ARC with long-term prior
AZT (ACTG 117)
ddI for people with AIDS or Advanced ARC who are intolerant to AZT
(ACTG 118)
ddI (2',3'-dideoxyinosine) for people with HIV dementia
rCD4-IgG Conjugate ("Designer Gene") and AZT
rCD4-IgG Conjugate ("Designer Gene")
CMV Retinitis protocols
Foscarnet for sight-threatening CMV Retinitis (ACTG 093)
Pneumocystis carinii Pneumonia (PCP) protocols
Aerosolized Pentamidine vs. Dapsone vs. Trimethoprim/Sulfamethoxazole
(Bactrim) in combination with AZT in ARC patients (ACTG 081)
Aerosolized Pentamidine vs. Trimethoprim/Sulfamethoxazole (Bactrim) in
combination with AZT in AIDS patients (ACTG 021)
Miscellaneous protocols
Coping Response in HIV infection
Foscarnet vs. Vidarabine to treat Acyclovir-resistant Herpes Simplex
(ACTG 095)
Neuropsychological testing
Previously covered protocols
Anti-retroviral protocols
CMV Retinitis protocols
Toxoplasmosis protocols
Miscellaneous protocols
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ANTI-RETROVIRAL PROTOCOLS
----------------------------------------
AZT AND ACYCLOVIR
DESCRIPTION: Study of early treatment with AZT (also known as Retrovir or
Zidovudine) and Acyclovir (Zovirax) in people with minimally symptomatic HIV
infection. In this phase III trial, all participants will receive AZT while
half will also receive acyclovir.
REQUIREMENTS: The participants in this study must be HIV positive with a T4
cell counts between 200 and 800 cells per cubic millimeter. In addition,
the participants must have had one or two of the following conditions:
shingles (herpes zoster); chronic or recurring skin rashes (seborrhea or
pruritic folliculitis); unexplained weight loss of greater than 10 pounds or
10 percent of body weight; unexplained persistent diarrhea; thrush; or oral
hairy leukaplakia (persistent generalized lymphadenopathy is permitted).
All participants must be 18 years or older. Persons requiring acyclovir
more than twice a year for recurring herpes are not eligible.
TERM: Two years
ADMINISTRATION: Half the participants will receive AZT and a placebo for
acyclovir while the other half will receive AZT and acyclovir. The AZT (100
mg) and acyclovir (800 mg) will be taken by mouth every four hours
(including a midnight dose). All participants are required to have blood
drawn and their symptoms checked during the initial screening. During the
first two months, participants will be required to return every two weeks
for monitoring. Thereafter, it will be on a monthly basis. Monitoring will
include testing for the level of p24 antigen and T4 cell counts. If T4 cell
counts drop below 200/mm^3 or the participant develops advanced ARC or AIDS,
they will be dropped from the study.
METHODOLOGY: This study will evaluate the ability of acyclovir to increase
the effectiveness of AZT. If acyclovir increases the effectiveness of AZT,
then lower doses of AZT could be used, reducing the side effects from high
doses of AZT. Acyclovir is commonly used to treat the herpes family of
viruses, and there has been some conjecture that Human Herpes Virus Six
(HHV-6) may act as a trigger to cause increased replication of HIV. Thus,
suppressing the herpes family of viruses could help slow HIV. AZT is a
Chain Terminator, which means it interferes with the ability of HIV to make
copies of itself during DNA replication (it stops the DNA "chain," and
prevents the next sections of DNA from linking in).
NOTES: Possible side effects of AZT include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. Acyclovir has some of the same side effects as
AZT, and also anorexia (loss of appetite).
CONTROLS: All participants will receive AZT. In addition, half will
receive a placebo, and the other half will receive acyclovir. The study is
randomized and double-blind, meaning that neither the participant nor their
doctor will know which participants are and are not receiving acyclovir.
ORGANIZATION: Georgetown University Hospital (Center for HIV Disease)
CONTACT: Dr. James Lavelle, Georgetown University Hospital, 3800 Reservoir
Road, N.W., Washington, DC 20007, (202) 687-8826
----------------------------------------
AZT & ACYCLOVIR, DDI, AND DDC COMBINATION STUDY
DESCRIPTION: This study is designed to assess the tolerance and toxicity of
the combination regimen of AZT/acyclovir, ddI, and ddC over a period of 12
months.
REQUIREMENTS: This study is for people with AIDS or severe ARC who HAVE NO
PRIOR EXPERIENCE WITH AZT, DDI, OR DDC FOR LONGER THAN A ONE WEEK PERIOD.
Participants must be off other anti-viral therapy for at least four weeks
before entering the study. All participants must have a CD4 count of less
than 350 cells/mm^3, and must not be anemic or have a low white blood count.
ARC patients must have either oral thrush or weight loss. People with
severe Kaposi's sarcoma or active opportunistic infections are excluded.
TERM: One year, all of which is outpatient, with possible extension of
therapy if it proves to be effective.
ADMINISTRATION: All drugs are taken orally (by mouth). For the first week,
participants take AZT every eight hours in combination with acyclovir every
eight hours. The second week, participants take ddI every 12 hours. The
third week, participants take ddC every eight hours. The cycle then repeats
with AZT and acyclovir again.
METHODOLOGY: All of the drugs used in this study have proven effectiveness
against HIV, but have some undesirable side effects. It is hoped that by
using the drugs in combination and rotating among them, the side effects of
any one drug will be so low as to be insignificant, and that the
effectiveness of the anti-HIV activity will be enhanced. By switching
between drugs, it is hoped that the chance of any "resistant" HIV strain
being able to build up a tolerance to a specific drug will be lowered.
AZT, ddI, and ddC all work the same way: they are "Chain Terminators." ddI
changes in your body to an activated form of ddA, a "fake" version of the
DNA base adenosine which doesn't let anything else chain onto it. This
means that when HIV tries to replicate itself by copying its RNA to DNA, the
"fake" ddA gets added to the DNA strand instead of real adenosine. ddA
doesn't have the necessary "hooks" for the next compound in the chain to
link into. The DNA strand just stops, halted in its tracks, incomplete and
ineffective. Similarly, AZT is the "fake" version of the base thymidine,
and ddC is the "fake" version of the base cytidine.
NOTES: Possible side effects of AZT include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. Acyclovir has some of the same side effects as
AZT, and also anorexia (loss of appetite). ddC has caused peripheral
neuropathy (pain in the extremities, like hands and feet) at higher doses.
This is reversible when the drug is stopped. Very early indications from
ddI show that at high dose levels it may also cause peripheral neuropathy,
but like ddC, the effects are reversible when the drug is stopped.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Laura Shay, R.N., or Kathy Marczyk, R.N., Building 10, Room
12C101, National Institutes of Health, Bethesda, MD 20892 (Medical Center
METRO stop). (301) 496-8959
----------------------------------------
DDC (2',3'-DIDEOXYCYTIDINE) VS. AZT (RETROVIR OR ZIDOVUDINE) IN PATIENTS
WITH ADVANCED ARC OR AIDS
DESCRIPTION: Phase III trial of ddC versus AZT in patients with advanced
ARC or AIDS. In this study, half of the participants will receive AZT and
half will receive ddC (2',3'-dideoxycytidine).
REQUIREMENTS: The participants in this study must have T4 cell counts below
200 cells per cubic millimeter and at least one of the following: a proven
episode of PCP within 120 days; unexplained fevers (with or without night
sweats) for 14 days; unexplained weight loss of at least 15 pounds or 10
percent of body weight; unexplained persistent diarrhea for 30 days; or
thrush. Participants must be able to care for their own needs, requiring at
most occasional assistance (a Karnofsky performance score measurement of at
least 60). Participants must have not taken AZT for more than 90 days prior
to entry into the study. All participants must be at least 18 years old.
TERM: Two years
ADMINISTRATION: Half the participants will receive AZT and half will
receive ddC. The AZT (200 mg every four hours), and ddC (0.75 mg every
eight hours), will be taken by mouth. Doses include a night time dose. All
participants are required to have blood drawn during the initial screening.
During the first ten weeks participants will be required to return every
week, and every two weeks thereafter. Monitoring will include testing the
p24 antigen levels and T4 cell counts.
METHODOLOGY: AZT and ddC are both "Chain Terminators," which means they
interfere with the ability of HIV to make copies of itself during DNA
replication (they stop the DNA "chain," and prevent the next sections of DNA
from linking in). AZT is a flawed version of the DNA base Thymidine, and
ddC is a flawed version of the base Cytidine. This study will compare the
effectiveness and side effects of ddC and AZT. Previous studies have shown
that ddC may be as effective or more effective than AZT in stopping HIV and
that it is not associated with lowering of red and white blood cell counts.
NOTES: Possible side effects of AZT include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. ddC has caused peripheral neuropathy (pain in
the extremities, like hands and feet) at higher doses. This is reversible
when the drug is stopped.
CONTROLS: Half of the participants will receive AZT and half will receive
ddC. The study is randomized and double-blind, meaning that neither the
participant nor their doctor will know which participants are receiving AZT
and which are receiving ddC.
ORGANIZATION: Georgetown University Hospital (Center for HIV Disease)
CONTACT: Dr. Phillip Pierce or Dr. James Lavelle, Georgetown University
Hospital, 3800 Reservoir Road, N.W., Washington, DC 20007, (202) 687-8672
or (202) 687-8826
----------------------------------------
DDI VS. AZT FOR PEOPLE WITH AIDS OR ADVANCED ARC WITH NO OR SHORT-TERM PRIOR
AZT (ACTG 116)
DESCRIPTION: Double-blind study of the effectiveness of ddI versus AZT for
people with AIDS or Advanced ARC, who have no prior experience or only
short-term prior experience taking AZT.
REQUIREMENTS: People with AIDS and eight weeks or less experience with AZT
must have had PNEUMOCYSTIS CARINII pneumonia (PCP) as their only AIDS-
defining opportunistic infection. People with AIDS and more than eight
weeks AZT experience can have had more than one episode of PCP, or any other
AIDS-defining opportunistic infection. People with Advanced ARC (AIDS-
related complex) must have had at least one of the following: oral
candiasis (thrush) during the past two years; oral hairy leukoplakia during
the past two years; unexplained temperature greater than or equal to 38.5oC
(101.3oF) for 14 consecutive days or for more than 15 days in any 30 day
period in the four months prior to entry; chronic diarrhea, defined as more
than three liquid stools per day that persists for more than 14 days without
a diagnosed cause, during the past two years; recurrent dermatomal zoster
(shingles) or zoster involving multiple dermatomes during the past two
years; weight loss in excess of 10 percent of body weight during the four
months prior to entry in the study. For people with ARC and less than eight
weeks experience with AZT, the above conditions must be fulfilled, and they
must also have CD4 cell counts less than or equal to 300 cells/mm^3 measured
on two separate occasions at least 72 hours apart, and the measurements must
be within 30 days of entry into the study. People with ARC and more than
eight weeks experience to AZT do not need to have symptoms now, as long as
they were present when AZT therapy was started; also, their CD4 cell counts
can be greater than 300 cells/mm^3 now as long as there is documentation
that they were less than or equal to 300 cells/mm^3 when AZT therapy was
started.
Participants for the study must be: at least 12 years of age, and people
between 12 and 18 must have written consent of their guardian; positive on
the ELISA test for HIV antibodies; able to care for most everyday needs
requiring only occasional assistance (a Karnofsky performance of 60).
Laboratory tests must be within certain limits within seven days before
starting the study (hemoglobin greater than or equal to 8.5 g/dl with no
blood transfusions in the preceding two weeks; neutrophil count greater than
or equal to 1000 cells/mm^3; platelet count greater than or equal to 75,000
platelets/mm^3; SGOT, SGPT, Alkaline Phosphase all less than or equal to
five times the upper limit of normal; creatinine less than or equal to 1.5
times the upper limit of normal; uric acid less than or equal to 9.0 mg/dl).
Women of child-bearing potential must have a negative pregnancy test within
14 days of the start of the study, and be willing to practice birth control
for the duration of the study.
Treatment for PNEUMOCYSTIS CARINII pneumonia must have ended at least two
weeks before beginning the study. Prophylaxis with aerosolized pentamidine
is REQUIRED (300 mg every four weeks) while on the study. People who have
previously received AZT must have not experienced a major intolerance
causing stopping of the AZT therapy at doses of at least 500 mg per day.
People with the following are excluded: known or suspected Kaposi's sarcoma
visceral disease (internal KS, not skin lesions) or KS that requires
chemotherapy; greater than or equal to stage two AIDS-dementia complex
(ADC); people who have received anti-HIV therapy other than AZT, or biologic
response modifiers, or corticosteroids within 30 days of the study, or
previous therapy with ribavirin within 90 days of the study; previous
therapy with gancicyclovir (DHPG); people who have been on AZT more than 48
weeks; neoplasms (cancer cells) other than basal cell (skin cancer) or IN-
SITU carcinoma of the cervix; women who are breast feeding; people with
grade two peripheral neuropathy; prior history of acute or chronic
pancreatitis; intractable diarrhea; history of seizures within the past six
months or currently requiring anti-convulsants for control; therapy within
the past 30 days with neurotoxic drugs; history of past or current heart
disease.
TERM: 18 months
ADMINISTRATION: Participants are randomly assigned to one of three groups:
the first group receives a 375 mg dose of ddI every 12 hours and a placebo
in place of AZT, taken every four hours; the second group receives a 250 mg
dose of ddI every 12 hours and a placebo in place of AZT, taken every four
hours; and the third group receives a 100 mg dose of AZT every four hours,
and a placebo in place of ddI every 12 hours. If the participant shows
toxicity to the drugs they are given, they will have the opportunity to
receive 100 mg of AZT, open-label, every four hours. If the participant
shows intolerance to AZT, there is then an option for them to receive open-
label ddI. Participants are expected to return for clinic visits every two
weeks for the first three months, and monthly for the remainder of the
study.
METHODOLOGY: AZT and ddI both work the same way: they are "Chain
Terminators." ddI changes in your body to an activated form of ddA, a
"fake" version of the DNA base adenosine which doesn't let anything else
chain onto it. This means that when HIV tries to replicate itself by
copying its RNA to DNA, the "fake" ddA gets added to the DNA strand instead
of real adenosine. ddA doesn't have the necessary "hooks" for the next
compound in the chain to link into. The DNA strand just stops, halted in
its tracks, incomplete and ineffective. Similarly, AZT is the "fake"
version of the base thymidine. This study is to determine the effectiveness
of ddI compared to AZT, and to see what are their relative level of side
effects.
NOTES: Possible side effects of AZT include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. Very early indications from ddI show that at
high dose levels it may cause peripheral neuropathy (pain in the
extremities, like hands and feet), but the effects appear to be reversible
when the drug is stopped. Buffering compounds included with ddI have also
been known to cause diarrhea. Other side effects of ddI may include
pancreatitis and increased uric acid levels.
CONTROLS: None. Participants are guaranteed to receive either AZT or ddI,
but since the study is a double-blind, neither the participant nor the
researcher will know who is on what.
ORGANIZATIONS: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH; and the Whitman-Walker Clinic.
CONTACTS: Barbara Lewis, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
Basil Vareldzis, Whitman-Walker Clinic, 1407 "S" Street, N.W., Washington,
DC 20009, (202) 797-3534
For hemophiliacs and people with other blood disorders, contact Stacy
Russell, George Washington University Hematology/Oncology Clinic, 2150
Pennsylvania Avenue, N.W., Washington, DC 20037, (202) 994-4200
----------------------------------------
DDI VS. AZT FOR PEOPLE WITH AIDS OR ADVANCED ARC WITH LONG-TERM PRIOR AZT
(ACTG 117)
DESCRIPTION: Double-blind study of the effectiveness of ddI versus AZT for
people with AIDS or Advanced ARC, who have at least 12 months prior
experience taking AZT.
REQUIREMENTS: People with AIDS can have had more than one episode of PCP,
or any other AIDS-defining opportunistic infection. People with Advanced
ARC (AIDS-related complex) must have had at least one of the following:
oral candiasis (thrush) during the past two years; oral hairy leukoplakia
during the past two years; unexplained temperature greater than or equal to
38.5oC (101.3oF) for 14 consecutive days or for more than 15 days in any 30
day period in the four months prior to entry; chronic diarrhea, defined as
more than three liquid stools per day that persists for more than 14 days
without a diagnosed cause, during the past two years; recurrent dermatomal
zoster (shingles) or zoster involving multiple dermatomes during the past
two years; weight loss in excess of 10 percent of body weight during the
four months prior to entry in the study; and CD4 cell counts less than or
equal to 300 cells/mm^3 measured on two separate occasions at least 72 hours
apart, within 30 days of entry into the study, and the most recent
measurement must be within 14 days.
Participants for the study must have been on AZT for at least 12 months,
with a minimum dose of 500 mg/day, and with no more than 60 days off AZT
therapy within the 12 month period (medical records must be provided).
Participants must also be: at least 12 years of age, and people between 12
and 18 must have written consent of their guardian; positive on the ELISA
test for HIV antibodies; able to care for most everyday needs requiring only
occasional assistance (a Karnofsky performance of 60); and be likely to be
available for follow-up for at least six months. Laboratory tests must be
within certain limits within seven days before starting the study
(hemoglobin greater than or equal to 8.5 g/dl with no blood transfusions in
the preceding two weeks; neutrophil count greater than or equal to 1000
cells/mm^3; platelet count greater than or equal to 75,000 platelets/mm^3;
SGOT, SGPT, Alkaline Phosphase all less than or equal to five times the
upper limit of normal; creatinine less than or equal to 1.5 times the upper
limit of normal; uric acid less than or equal to 9.0 mg/dl). Women of
child-bearing potential must have a negative pregnancy test within 14 days
of the start of the study, and be willing to practice birth control for the
duration of the study. Treatment for PNEUMOCYSTIS CARINII pneumonia must
have ended at least two weeks before beginning the study. Prophylaxis with
aerosolized pentamidine is REQUIRED (300 mg every four weeks) while on the
study.
People with the following are excluded: people who have received anti-HIV
therapy other than AZT, or cytotoxic agents (excluding intralesion agents),
biologic response modifiers, or corticosteroids within 30 days of the study,
or previous therapy with ribavirin within 90 days of the study; active
alcohol or drug abuse; psychological or emotional problems sufficient to
prevent adequate compliance with the study; women who are breast feeding;
transfusion within 30 days prior to entry in the study; intractable
diarrhea; previous therapy with known or suspected Kaposi's sarcoma visceral
disease (internal KS, not skin lesions) or KS that requires chemotherapy;
greater than or equal to stage two AIDS-dementia complex (ADC); neoplasms
(cancer cells) other than basal cell (skin cancer) or IN-SITU carcinoma of
the cervix; people with grade two peripheral neuropathy; prior history of
acute or chronic pancreatitis; history of seizures within the past six
months or currently requiring anti-convulsants for control; therapy within
the past 30 days with neurotoxic drugs; history of past or current heart
disease; presence of a malignancy likely to require chemotherapy during the
study; life expectancy less than three months.
TERM: 18 months
ADMINISTRATION: Participants are randomly assigned to one of three groups:
the first group receives a 375 mg dose of ddI every 12 hours and a placebo
in place of AZT, taken every four hours; the second group receives a 250 mg
dose of ddI every 12 hours and a placebo in place of AZT, taken every four
hours; and the third group receives a 100 mg dose of AZT every four hours,
and a placebo in place of ddI every 12 hours. If the participant shows
toxicity to the drugs they are given, they will have the opportunity to
receive 100 mg of AZT, open-label, every four hours. If the participant
shows intolerance to AZT, there is then an option for them to receive open-
label ddI. Participants are expected to return for clinic visits every two
weeks, for the first three months, and monthly for the remainder of the
study.
METHODOLOGY: AZT and ddI both work the same way: they are "Chain
Terminators." ddI changes in your body to an activated form of ddA, a
"fake" version of the DNA base adenosine which doesn't let anything else
chain onto it. This means that when HIV tries to replicate itself by
copying its RNA to DNA, the "fake" ddA gets added to the DNA strand instead
of real adenosine. ddA doesn't have the necessary "hooks" for the next
compound in the chain to link into. The DNA strand just stops, halted in
its tracks, incomplete and ineffective. Similarly, AZT is the "fake"
version of the base thymidine. This study is to determine the effectiveness
of ddI compared to AZT, and to see what are their relative level of side
effects.
NOTES: Possible side effects of AZT include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. Very early indications from ddI show that at
high dose levels it may cause peripheral neuropathy (pain in the
extremities, like hands and feet), but the effects appear to be reversible
when the drug is stopped. Buffering compounds included with ddI have also
been known to cause diarrhea. Other side effects of ddI may include
pancreatitis and increased uric acid levels.
CONTROLS: None. Participants are guaranteed to receive either AZT or ddI,
but since the study is double-blind, neither the participant nor the
researcher will know who is on what.
ORGANIZATIONS: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH; and the Whitman-Walker Clinic.
CONTACTS: Barbara Lewis, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
Basil Vareldzis, Whitman-Walker Clinic, 1407 "S" Street, N.W., Washington,
DC 20009, (202) 797-3534
For hemophiliacs and people with other blood disorders, contact Stacy
Russell, George Washington University Hematology/Oncology Clinic, 2150
Pennsylvania Avenue, N.W., Washington, DC 20037, (202) 994-4200
----------------------------------------
DDI FOR PEOPLE WITH AIDS OR ADVANCED ARC WHO ARE INTOLERANT TO AZT (ACTG
118)
DESCRIPTION: Study of the effectiveness of ddI for people with AIDS or
Advanced ARC, who are intolerant of AZT.
REQUIREMENTS: People with AIDS can have had more than one episode of PCP,
or any other AIDS-defining opportunistic infection. People with Advanced
ARC (AIDS-related complex) must have had at least one of the following:
oral candiasis (thrush) during the past two years; oral hairy leukoplakia
during the past two years; unexplained temperature greater than or equal to
38.5oC (101.3oF) for 14 consecutive days or for more than 15 days in any 30
day period in the four months prior to entry; chronic diarrhea, defined as
more than three liquid stools per day that persists for more than 14 days
without a diagnosed cause, during the past two years; recurrent single
dermatomal zoster (shingles) or zoster episode involving multiple dermatomes
during the past two years; weight loss in excess of 10 percent of body
weight during the four months prior to entry in the study; and CD4 cell
counts less than or equal to 300 cells/mm^3 measured on two separate
occasions at least 72 hours apart, within 30 days of entry into the study,
and the most recent measurement must be within 14 days.
Participants for the study must have been intolerant of AZT during at least
two courses of treatment (one of which had to have been at a daily dose of
600 mg of AZT or less), with the intolerance demonstrated by an AZT-related
decrease in hemoglobin levels of at least two g/dl to levels less than or
equal to nine g/dl, or AZT-related depression of neutrophils of at least 200
cells/mm^3 to less than 750 cells/mm^3. Participants must also be: at
least 12 years or age, and people between 12 and 18 must have written
consent of their guardian; positive on the ELISA test for HIV antibodies;
able to care for most everyday needs requiring only occasional assistance (a
Karnofsky performance of 60); and be likely to be available for follow-up
for at least six months. Laboratory tests must be within certain limits
within seven days before starting the study (hemoglobin greater than or
equal to 8.5 g/dl with no blood transfusions in the preceding two weeks;
neutrophil count greater than or equal to 750 cells/mm^3; platelet count
greater than or equal to 50,000 platelets/mm^3; SGOT, SGPT, Alkaline
Phosphase all less than or equal to five times the upper limit of normal;
creatinine less than or equal to 1.5 times the upper limit of normal; uric
acid less than or equal to 7.5 mg/dl; White Blood Cell (WBC) count greater
than or equal to 1000 cells/mm^3). Women of child-bearing potential must
have a negative pregnancy test within 14 days of the start of the study, and
be willing to practice birth control for the duration of the study.
Treatment for PNEUMOCYSTIS CARINII pneumonia must have ended at least two
weeks before beginning the study. Prophylaxis with aerosolized pentamidine
is REQUIRED (300 mg every four weeks) while on the study. Bactrim or
Dapsone are allowed for PCP prophylaxis if intolerance to aerosolized
pentamidine can be demonstrated.
People with the following are excluded: people who have received anti-HIV
therapy other than AZT, or cytotoxic agents (excluding intralesion agents),
biologic response modifiers, or corticosteroids within 30 days of the study,
or previous therapy with ribavirin within 90 days of the study; active
alcohol or drug abuse; psychological or emotional problems sufficient to
prevent adequate compliance with the study; women who are breast feeding;
transfusion within 30 days prior to entry in the study; intractable
diarrhea; previous therapy with known or suspected Kaposi's sarcoma visceral
disease (internal KS, not skin lesions) or KS that requires chemotherapy;
greater than or equal to stage two AIDS-dementia complex (ADC); neoplasms
(cancer cells) other than basal cell (skin cancer) or IN-SITU carcinoma of
the cervix; people with grade two peripheral neuropathy; prior history of
acute or chronic pancreatitis; history of seizures within the past six
months or currently requiring anti-convulsants for control; therapy within
the past 30 days with neurotoxic drugs; history of past or current heart
disease; presence of a malignancy likely to require chemotherapy during the
study; life expectancy less than six months.
TERM: 18 months
ADMINISTRATION: Participants are randomly assigned to one of three groups,
receiving a 375 mg, 250 mg, or a 100 mg dose of ddI every 12 hours.
Participants are expected to return for clinic visits every two weeks for
the first three months, and monthly for the remainder of the study.
METHODOLOGY: ddI is a "Chain Terminator." ddI changes in your body to an
activated form of ddA, a "fake" version of the DNA base adenosine which
doesn't let anything else chain onto it. This means that when HIV tries to
replicate itself by copying its RNA to DNA, the "fake" ddA gets added to the
DNA strand instead of real adenosine. ddA doesn't have the necessary
"hooks" for the next compound in the chain to link into. The DNA strand
just stops, halted in its tracks, incomplete and ineffective. Because ddI
is handled differently by the body than AZT, it is hoped that it will still
be effective, with no or lower side effects, than AZT in people who are
intolerant to AZT.
NOTES: Very early indications from ddI show that at high dose levels it may
cause peripheral neuropathy (pain in the extremities, like hands and feet),
but the effects appear to be reversible when the drug is stopped. Buffering
compounds included with ddI have also been known to cause diarrhea. Other
side effects of ddI may include pancreatitis and increased uric acid levels.
CONTROLS: None. Participants are guaranteed to receive one of three dose
levels of ddI.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units (ATEUs) run by NIH.
CONTACTS: Barbara Lewis, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
For hemophiliacs and people with other blood disorders, contact Stacy
Russell, George Washington University Hematology/Oncology Clinic, 2150
Pennsylvania Avenue, N.W., Washington, DC 20037, (202) 994-4200
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DDI (2',3'-DIDEOXYINOSINE) FOR PEOPLE WITH HIV DEMENTIA
DESCRIPTION: Phase I Study of drug to fight HIV.
REQUIREMENTS: This study is for people with AIDS or severe ARC and who have
HIV-related dementia, particularly people who HAVE NOT BEEN ON AZT OR HAVE
BEEN ON AZT FOR SIX WEEKS OR LESS. Participants must be off AZT and other
anti-viral therapy for at least four weeks before the study. All
participants must have a count of less than 350 T4 cells per ml, and must
not be anemic or have a low white blood count. ARC patients must have
either oral thrush or weight loss. People with severe Kaposi's sarcoma or
active opportunistic infections are excluded.
TERM: The initial phase lasts for a total of 13 months; two days as an
inpatient and 12 1/2 months as an outpatient. If the initial results prove
favorable, it is possible that permission will be obtained from the FDA to
continue the study for a longer period of time.
ADMINISTRATION: On the first day, the drug will be given once
intravenously; on the second day, the drug will be given once orally. The
patient will then take the drug by mouth two times a day as an outpatient.
The patient will be required to return to NIH once a week for monitoring for
the first six weeks as an outpatient. After that, the patient will come to
clinic every two weeks for six weeks, then every three weeks while on the
study. With a Phase I Study, everything is very much up in the air and
subject to negotiation and changes as the study progresses. At completion
of the study, patients can either be transferred to other treatment
protocols if they are eligible, or drop out, at their option.
METHODOLOGY: ddI is a Chain Terminator. ddI changes in your body to an
activated form of ddA, a "fake" version of adenosine which doesn't let
anything else chain onto it. This means that when HIV tries to replicate
itself by copying its RNA to DNA, the "fake" ddA gets added to the DNA
strand instead of real adenosine. ddA doesn't have the necessary "hooks"
for the next compound in the chain to link into. The DNA strand just stops,
halted in its tracks, incomplete and ineffective. ddI is handled by the
body differently than AZT, and it appears to be less toxic for bone-marrow
cells than AZT (in the test tube).
NOTES: Preliminary results with another form of this drug, ddA, indicated
that, at the doses tested, it could be tolerated for up to eight weeks
without major side effects (toxicity problems). Some patients on ddA had
increases in their T4 cell counts. ddA is converted in the body to ddI, and
as mentioned above, ddI is converted back again to an activated form of ddA,
so it is likely that similar therapeutic results will be obtained with ddI.
The doses that will be tested in this study are similar to the doses that
have already been tested with ddA.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drug.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328
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RCD4-IGG CONJUGATE ("DESIGNER GENE") AND AZT
DESCRIPTION: Study to compare the effects of giving recombinant CD4 (rCD4)
with attached Immunoglobulin G (the so-called "Designer Gene") at two
different doses levels alone, and in combination with AZT (Zidovudine or
Retrovir), in the treatment of HIV infection in people who do not have AIDS.
REQUIREMENTS: Participants must: be positive for HIV on the ELISA and
Western Blot tests; have a CD4 count between 200 and 500/mm^3; have the
percentage of CD4 cells be greater than 20 percent of circulating
lymphocytes; have not been on any other investigational drugs within four
weeks of entering the study; be willing to abstain from all other
experimental therapy for HIV infection during the course of the study; and
have laboratory tests within certain limits (EKG normal; B.U.N. less than or
equal to 30 mg/dl; serum creatinine less than or equal to two mg/dl; urine
protein less than 2+ by dipstick or less than one gram/24 hours;
transaminases less than two times the upper limit of normal; alkaline
phosphatase less than two times the upper limit of normal; hemoglobin
greater than or equal to 10 mg/dl; granulocytes greater than or equal to
1500/mm^3; platelets greater than or equal to 100,000/mm^3).
TERM: 14 weeks, with possible additional maintenance period of 12 weeks.
ADMINISTRATION: Participants are divided into four groups: the first group
will receive a single injection of 100 micrograms/kg of rCD4-IgG, followed
by a two week wait, followed by 12 weeks of 100 micrograms/kg of rCD4-IgG
given once per week by subcutaneous injection (injecting under the skin).
The second group will receive the same treatment as the first group, and 100
mg of AZT every four hours in addition, with the night-time dose omitted
(AZT is continuous, even during the two week wait period). The third group
is like the first group, but with a dosage of 300 micrograms/kg of rCD4-IgG.
The fourth group is like the third group, but with the addition of 100 mg of
AZT every four hours, with the night-time dose omitted.
This study will require two pre-study evaluations, clinic visits on two
consecutive days after the first dose of rCD4-IgG, and then weekly visits
for the duration of the study.
METHODOLOGY: rCD4 is a genetically-engineered version of the compound which
is on the surface of CD4 (T4) cells, however there is no actual CD4 cell
underneath it. Since HIV is a virus, and needs to attack, invade, and take
over another living cell in order to reproduce, it is hoped that if HIV
binds to rCD4 instead of actual CD4 cells, it will find itself attached to
something which cannot help it reproduce, and it will thus be rendered
ineffective. To assist in this, the rCD4 is chemically bound to
Immunoglobulin G, which is a "marker" produced by the body which tells the
rest of the immune system which foreign cells to kill. The combination
(conjugate) of rCD4 and IgG will hopefully provide the equivalent of
grabbing the virus to prevent it from doing damage, and hanging a "Kill Me"
sign on its back.
NOTES: This is no cost to the patient for the pre-study evaluations,
monitoring, or medications. NIH will pay travel costs within the U.S. for
patients enrolled on the study who live more than 150 miles from NIH.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID), Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B13, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
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