Sarcoma, KaposiPhase 1NCT00000681
A Phase I Study of the Combination of Recombinant GM-CSF, AZT, and Chemotherapy (ABV) (Adriamycin, Bleomycin, Vincristine) in AIDS and Kaposi's Sarcoma
A Phase 1 study testing Bleomycin sulfate, Vincristine sulfate and Doxorubicin hydrochloride in people with Sarcoma, Kaposi and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial summary
To determine the safety as well as the most effective dose of sargramostim (GM-CSF; granulocyte-macrophage colony stimulating factor) that will prevent the side effects caused by the combined use of zidovudine (AZT) and various doses of cancer-fighting drugs (doxorubicin, bleomycin, and vincristine) in AIDS patients… Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Sarcoma, Kaposi, HIV Infections
- What is being tested?
- Bleomycin sulfate, Vincristine sulfate and Doxorubicin hydrochloride
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- Start not givento Oct 1993
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- Non-steroidal agents such as acetaminophen for drug-related fevers.
- Pentamidine inhalation prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients with a prior history or a T4 count < 200 cells/mm3.
- Antiemetics for nausea, vomiting.
- Symptomatic treatment for grades 1 and 2 oral toxicity.
- Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).
- Patients must have newly diagnosed biopsy-proven advanced AIDS-related Kaposi's sarcoma.
Who cannot join
- Concurrent Medication:
- Excluded:
- Systemic steroids for > 1 week in any 30 days.
- All known marrow-suppressive agents.
- Any other investigational drugs.
- Patients will be excluded from the study for the following reasons:
Show all 24Show fewer
- The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer.
- Alteration of mental status that may not permit compliance with the protocol.
- Symptomatic sensory or motor neuropathy.
- History of myocardial infarction or significant arrhythmias.
- Class III/IV functional capacity in cardiac patients.
- Prior Medication:
- Excluded:
- Cytotoxic chemotherapy.
- Excluded within 1 week of study entry:
- Therapy for Kaposi's sarcoma, including interferons, immunomodulators, antiretroviral agents.
- Patients may not have any of the following diseases or symptoms:
- Allergy to bleomycin.
- The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer.
- Alteration of mental status that may not permit compliance with the protocol.
- Symptomatic sensory or motor neuropathy.
- History of myocardial infarction or significant arrhythmias.
- Class III/IV functional capacity in cardiac patients.
- Concurrent serious infections, such as Pneumocystis carinii pneumonia (PCP), toxoplasma brain abscess, cytomegalovirus (CMV) retinitis or colitis, cryptococcal meningitis, and symptomatic Mycobacterium avium- intracellulare (MAI).
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215
USC CRS
Los Angeles, California, 900331079
UCLA CARE Center CRS
Los Angeles, California, 90095
Pitt CRS
Pittsburgh, Pennsylvania, 15213
About this study
To determine the safety as well as the most effective dose of sargramostim (GM-CSF; granulocyte-macrophage colony stimulating factor) that will prevent the side effects caused by the combined use of zidovudine (AZT) and various doses of cancer-fighting drugs (doxorubicin, bleomycin, and vincristine) in AIDS patients with Kaposi's sarcoma (KS).
Patients included in this study have KS, which is a type of cancer that occurs in nearly 20 percent of patients with AIDS. AIDS patients with extensive KS require treatment with effective cytotoxic (anti-cancer) agents to reduce the tumor size and with antiretroviral agents such as AZT to prevent or ameliorate the development of opportunistic infections. Due to the significant toxic effect of both cytotoxic and antiviral agents on the bone marrow where new blood cells are generated, the combination of these agents is expected to result in complications such as granulocytopenia (very low granulocyte counts). Hematopoietic growth factors such as GM-CSF may reduce the severity and duration of marrow suppression. This may improve survival. Clinical trials of GM-CSF in HIV infected individuals with or without granulocytopenia have shown that the progenitor cells (early blood cells) are responsive to GM-CSF.
Read the detailed description
Patients included in this study have KS, which is a type of cancer that occurs in nearly 20 percent of patients with AIDS. AIDS patients with extensive KS require treatment with effective cytotoxic (anti-cancer) agents to reduce the tumor size and with antiretroviral agents such as AZT to prevent or ameliorate the development of opportunistic infections. Due to the significant toxic effect of both cytotoxic and antiviral agents on the bone marrow where new blood cells are generated, the combination of these agents is expected to result in complications such as granulocytopenia (very low granulocyte counts). Hematopoietic growth factors such as GM-CSF may reduce the severity and duration of marrow suppression. This may improve survival. Clinical trials of GM-CSF in HIV infected individuals with or without granulocytopenia have shown that the progenitor cells (early blood cells) are responsive to GM-CSF.
AMENDED 910222 Due to continued concerns about GM-CSF toxicities seen in the 5 mcg/kg GM-CSF with 20 mg/m2 adriamycin/BV/AZT cohort, the GM-CSF dose in this study has been reduced while the adriamycin dose escalation will continue.
AMENDED 900430 Dosages for AZT and GM-CSF changed to reflect ongoing results. Original design: Patients receive the combination of AZT, antineoplastic chemotherapy, and GM-CSF in groups of three patients each. The first group receives baseline doses, and if the treatment is well tolerated, the subsequent groups of patients receive higher doses of the chemotherapy, in which the dose of doxorubicin is increased while bleomycin, vincristine, and AZT doses remain fixed throughout the study. The dose of all drugs remains fixed for a given patient. The anticancer drugs are given intravenously every 2 weeks. AZT is given every 4 hours by mouth. GM-CSF is self-injected subcutaneously every day from day 2 - day 12 of each treatment cycle. Patients repeat the chemotherapy every 2 weeks, for a maximum of seven cycles, with AZT being given continuously. When the maximum tolerated dose (MTD) of chemotherapy combined with GM-CSF is determined, the next phase of the study begins. Again the dose of chemotherapy is increased in groups of patients, but the every-day dose of GM-CSF is increased. Again, these chemotherapy cycles are repeated every 2 weeks up to a maximum of seven cycles. Patients receive physician examination and laboratory tests every week during the study and again at 4 weeks after the study. AMENDED: Dosages for AZT and GM-CSF have been changed to reflect ongoing results.
- Conditions
- Sarcoma, Kaposi, HIV Infections
- Being tested
- Bleomycin sulfate, Vincristine sulfate, Doxorubicin hydrochloride, Zidovudine, Sargramostim
- Keywords
- Vincristine, Doxorubicin, Drug Evaluation, Drug Therapy, Combination, Granulocyte-Macrophage Colony-Stimulating Factor, Acquired Immunodeficiency Syndrome, Zidovudine, Bleomycin
- Medical subject headings
- Sarcoma, Kaposi, HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bleomycin sulfateDrug
ZidovudineDrug
SargramostimDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionOct 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sarcoma, KaposiStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 24 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Gill PS, Study chairMiles S, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000681
- Sponsor's protocol ID
- ACTG 094
- Other IDs
- 11069
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 3 Nov 2021
- Results posted
- No
Publications
Gill PS, Bernstein-Singer M, Espina BM, Rarick M, Magy F, Montgomery T, Berry MS, Levine A. Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma. AIDS. 1992 Dec;6(12):1477-81. doi: 10.1097/00002030-199212000-00009.
PubMed 1283520
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Combination of Recombinant GM-CSF, AZT, and Chemotherapy (ABV) (Adriamycin, Bleomycin, Vincristine) in AIDS and Kaposi's Sarcoma
- ClinicalTrials.gov ID
- NCT00000681
- Acronym / sponsor ID
- ACTG 094
- Conditions
- Sarcoma, Kaposi, HIV Infections
- Keywords
- Vincristine, Doxorubicin, Drug Evaluation, Drug Therapy, Combination, Granulocyte-Macrophage Colony-Stimulating Factor, Acquired Immunodeficiency Syndrome, Zidovudine, Bleomycin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Oct 1993 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the safety as well as the most effective dose of sargramostim (GM-CSF; granulocyte-macrophage colony stimulating factor) that will prevent the side effects caused by the combined use of zidovudine (AZT) and various doses of cancer-fighting drugs (doxorubicin, bleomycin, and vincristine) in AIDS patients with Kaposi's sarcoma (KS).
Patients included in this study have KS, which is a type of cancer that occurs in nearly 20 percent of patients with AIDS. AIDS patients with extensive KS require treatment with effective cytotoxic (anti-cancer) agents to reduce the tumor size and with antiretroviral agents such as AZT to prevent or ameliorate the development of opportunistic infections. Due to the significant toxic effect of both cytotoxic and antiviral agents on the bone marrow where new blood cells are generated, the combination of these agents is expected to result in complications such as granulocytopenia (very low granulocyte counts). Hematopoietic growth factors such as GM-CSF may reduce the severity and duration of marrow suppression. This may improve survival. Clinical trials of GM-CSF in HIV infected individuals with or without granulocytopenia have shown that the progenitor cells (early blood cells) are responsive to GM-CSF.
Detailed description
Patients included in this study have KS, which is a type of cancer that occurs in nearly 20 percent of patients with AIDS. AIDS patients with extensive KS require treatment with effective cytotoxic (anti-cancer) agents to reduce the tumor size and with antiretroviral agents such as AZT to prevent or ameliorate the development of opportunistic infections. Due to the significant toxic effect of both cytotoxic and antiviral agents on the bone marrow where new blood cells are generated, the combination of these agents is expected to result in complications such as granulocytopenia (very low granulocyte counts). Hematopoietic growth factors such as GM-CSF may reduce the severity and duration of marrow suppression. This may improve survival. Clinical trials of GM-CSF in HIV infected individuals with or without granulocytopenia have shown that the progenitor cells (early blood cells) are responsive to GM-CSF.
AMENDED 910222 Due to continued concerns about GM-CSF toxicities seen in the 5 mcg/kg GM-CSF with 20 mg/m2 adriamycin/BV/AZT cohort, the GM-CSF dose in this study has been reduced while the adriamycin dose escalation will continue.
AMENDED 900430 Dosages for AZT and GM-CSF changed to reflect ongoing results. Original design: Patients receive the combination of AZT, antineoplastic chemotherapy, and GM-CSF in groups of three patients each. The first group receives baseline doses, and if the treatment is well tolerated, the subsequent groups of patients receive higher doses of the chemotherapy, in which the dose of doxorubicin is increased while bleomycin, vincristine, and AZT doses remain fixed throughout the study. The dose of all drugs remains fixed for a given patient. The anticancer drugs are given intravenously every 2 weeks. AZT is given every 4 hours by mouth. GM-CSF is self-injected subcutaneously every day from day 2 - day 12 of each treatment cycle. Patients repeat the chemotherapy every 2 weeks, for a maximum of seven cycles, with AZT being given continuously. When the maximum tolerated dose (MTD) of chemotherapy combined with GM-CSF is determined, the next phase of the study begins. Again the dose of chemotherapy is increased in groups of patients, but the every-day dose of GM-CSF is increased. Again, these chemotherapy cycles are repeated every 2 weeks up to a maximum of seven cycles. Patients receive physician examination and laboratory tests every week during the study and again at 4 weeks after the study. AMENDED: Dosages for AZT and GM-CSF have been changed to reflect ongoing results.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Non-steroidal agents such as acetaminophen for drug-related fevers.
- Pentamidine inhalation prophylaxis for Pneumocystis carinii pneumonia (PCP) in patients with a prior history or a T4 count < 200 cells/mm3.
- Antiemetics for nausea, vomiting.
- Symptomatic treatment for grades 1 and 2 oral toxicity.
- Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).
Key exclusion criteria (24 listed)
- Systemic steroids for > 1 week in any 30 days.
- All known marrow-suppressive agents.
- Any other investigational drugs.
- The presence of other active malignancies except basal cell carcinoma of the skin and in situ uterine cancer.
- Alteration of mental status that may not permit compliance with the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bleomycin sulfate | Drug | – |
| Vincristine sulfate | Drug | – |
| Doxorubicin hydrochloride | Drug | – |
| Zidovudine | Drug | – |
| Sargramostim | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
- Background: PubMed 1283520Gill PS, Bernstein-Singer M, Espina BM, Rarick M, Magy F, Montgomery T, Berry MS, Levine A. Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma. AIDS. 1992 Dec;6(12):1477-81. doi: 10.1097/00002030-199212000-00009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gill PS study chair
Miles S study chair
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bleomycin sulfate, Vincristine sulfate and Doxorubicin hydrochloride in people with Sarcoma, Kaposi and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2021.