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A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma

Primary Purpose

Sarcoma, Kaposi, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Interferon alfa-2b
Zidovudine
Sargramostim
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma, Kaposi focused on measuring Interferon Alfa-2b, Immune System, Drug Evaluation, Drug Therapy, Combination, Granulocyte-Macrophage Colony-Stimulating Factor, Acquired Immunodeficiency Syndrome, Zidovudine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Prophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine. Ibuprofen, not to exceed 1600 mg/day, for fever or analgesia. Biopsy-proven Kaposi's sarcoma confined to the skin, lymph nodes, or non-nodular lesions of the hard palate. Positive antibody to HIV confirmed by any federally licensed ELISA test kit. Patients must be able to give informed consent. Allowed: Basal cell carcinoma. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks). Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions. Severe (> 2+) tumor-associated edema. Concurrent neoplasia (excluding basal cell carcinoma). Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction o significant cardiac arrhythmias. Dementia (= or > stage 2). Concurrent Medication: Excluded: Any systemic chemoprophylaxis not specifically allowed. Aspirin and acetaminophen. Nonsteroidal anti-inflammatory agents not specifically allowed. Corticosteroids. Barbiturates. Other antiviral agents, immunotherapy, hormonal therapy, chemotherapy directed at treatment of viral infection or malignancy. Other investigational agents. Concurrent Treatment: Excluded: Radiation therapy directed at treatment of viral infection or malignancy. Patients with the following are excluded: Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks). Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions. Severe (> 2+) tumor-associated edema. Concurrent neoplasia (excluding basal cell carcinoma). Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction or significant cardiac arrhythmias. Dementia (= or > stage 2). Prior Medication: Excluded: Interferon alpha-2b. Granulocyte-macrophage colony-stimulating factor (GM-CSF). Prior grade 3 or grade 4 toxicity during AZT therapy. Excluded within 30 days of study entry: Zidovudine (AZT). Corticosteroids. Biologic response modifiers. Cytotoxic chemotherapy. Antiretroviral agents. Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults). Prior Treatment: Excluded within 30 days of study entry: Requirement for red blood cell transfusions within 30 days of study entry. Radiation therapy. Active drug or alcohol abuse.

Sites / Locations

  • Mem Sloan - Kettering Cancer Ctr

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000694
Brief Title
A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma
Official Title
A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 1992 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
To define the best doses of sargramostim ( granulocyte-macrophage colony-stimulating factor; GM-CSF ), interferon alfa-2b ( IFN-A2b ), and zidovudine ( AZT ) to give together in patients with AIDS-associated Kaposi's sarcoma ( KS ), to learn about the side effects of these drugs when they are given together for 8 weeks, and to find out whether the combination of GM-CSF, IFN-A2b, and AZT has any effect on KS, HIV, or the immune system. Studies show that IFN-A2b can cause KS tumors to shrink or disappear in about 30 percent of patients. IFN-A2b can greatly reduce the growth of the HIV virus in test tube experiments and perhaps in patients. AZT has also been shown to reduce the growth of HIV and show improvements in the immune system with fewer infections. Test tube experiments show that when IFN-A2b and AZT are used together, they reduce the growth of the HIV virus much more effectively than when either drug is used alone. In recent studies of the combination of interferon alpha and AZT in patients with KS, more than 40 percent of the patients showed shrinkage of their tumors, and some showed evidence for suppression of HIV growth in the body. However, the combination of IFN-A2b with AZT often caused a marked lowering of the white blood cell (WBC) count, especially a type of WBC called the granulocyte (or neutrophil) which is important in the body's defense against infection. Recombinant human GM-CSF is a human protein which is produced in bacteria. It has been shown to cause an increase in the WBC count.
Detailed Description
Studies show that IFN-A2b can cause KS tumors to shrink or disappear in about 30 percent of patients. IFN-A2b can greatly reduce the growth of the HIV virus in test tube experiments and perhaps in patients. AZT has also been shown to reduce the growth of HIV and show improvements in the immune system with fewer infections. Test tube experiments show that when IFN-A2b and AZT are used together, they reduce the growth of the HIV virus much more effectively than when either drug is used alone. In recent studies of the combination of interferon alpha and AZT in patients with KS, more than 40 percent of the patients showed shrinkage of their tumors, and some showed evidence for suppression of HIV growth in the body. However, the combination of IFN-A2b with AZT often caused a marked lowering of the white blood cell (WBC) count, especially a type of WBC called the granulocyte (or neutrophil) which is important in the body's defense against infection. Recombinant human GM-CSF is a human protein which is produced in bacteria. It has been shown to cause an increase in the WBC count. AMENDED: 900910 to allow one patient to be treated beyond one year. Original design: GM-CSF, IFN-A2b, and AZT are given every day for 8 weeks. There are 6 patients per dose level. IFN-A2b and GM-CSF are given in two separate injections under the skin (subcutaneous injection) once a day. AZT is given orally every 4 hours (6 times/day). The first patients are given doses of the drugs that are quite well tolerated when given alone. If these dosages are tolerated without serious side effects, the dosage of IFN-A2b is increased in subsequent groups of patients. Maintenance treatment consisting of the same dose received at the conclusion of the initial 8 week course of treatment will be resumed with eligible patients for up to 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Kaposi, HIV Infections
Keywords
Interferon Alfa-2b, Immune System, Drug Evaluation, Drug Therapy, Combination, Granulocyte-Macrophage Colony-Stimulating Factor, Acquired Immunodeficiency Syndrome, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
18 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Interferon alfa-2b
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Sargramostim

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Prophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine. Ibuprofen, not to exceed 1600 mg/day, for fever or analgesia. Biopsy-proven Kaposi's sarcoma confined to the skin, lymph nodes, or non-nodular lesions of the hard palate. Positive antibody to HIV confirmed by any federally licensed ELISA test kit. Patients must be able to give informed consent. Allowed: Basal cell carcinoma. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks). Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions. Severe (> 2+) tumor-associated edema. Concurrent neoplasia (excluding basal cell carcinoma). Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction o significant cardiac arrhythmias. Dementia (= or > stage 2). Concurrent Medication: Excluded: Any systemic chemoprophylaxis not specifically allowed. Aspirin and acetaminophen. Nonsteroidal anti-inflammatory agents not specifically allowed. Corticosteroids. Barbiturates. Other antiviral agents, immunotherapy, hormonal therapy, chemotherapy directed at treatment of viral infection or malignancy. Other investigational agents. Concurrent Treatment: Excluded: Radiation therapy directed at treatment of viral infection or malignancy. Patients with the following are excluded: Prior or concurrent opportunistic infection or B symptoms (unexplained fever, night sweats, > 10 percent involuntary weight loss or diarrhea persisting > 2 weeks). Visceral (non-nodal) Kaposi's sarcoma including extensive oral lesions. Severe (> 2+) tumor-associated edema. Concurrent neoplasia (excluding basal cell carcinoma). Significant cardiac disease (New York Heart Association class III or IV) or history of myocardial infarction or significant cardiac arrhythmias. Dementia (= or > stage 2). Prior Medication: Excluded: Interferon alpha-2b. Granulocyte-macrophage colony-stimulating factor (GM-CSF). Prior grade 3 or grade 4 toxicity during AZT therapy. Excluded within 30 days of study entry: Zidovudine (AZT). Corticosteroids. Biologic response modifiers. Cytotoxic chemotherapy. Antiretroviral agents. Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults). Prior Treatment: Excluded within 30 days of study entry: Requirement for red blood cell transfusions within 30 days of study entry. Radiation therapy. Active drug or alcohol abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
SE Krown
Official's Role
Study Chair
Facility Information:
Facility Name
Mem Sloan - Kettering Cancer Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
1634925
Citation
Krown SE, Paredes J, Bundow D, Polsky B, Gold JW, Flomenberg N. Interferon-alpha, zidovudine, and granulocyte-macrophage colony-stimulating factor: a phase I AIDS Clinical Trials Group study in patients with Kaposi's sarcoma associated with AIDS. J Clin Oncol. 1992 Aug;10(8):1344-51. doi: 10.1200/JCO.1992.10.8.1344.
Results Reference
background
Citation
Krown SE, Paredes J, Bundow D, Flomenberg N. Combination therapy with interferon-alpha (IFN-alpha), zidovudine (AZT), and recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF): a phase I trial in patients with AIDS-associated Kaposi's sarcoma. Int Conf AIDS. 1990 Jun 20-23;6(3):214 (abstract no SB513)
Results Reference
background

Learn more about this trial

A Phase I Trial of Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor (rHuGM-CSF), Recombinant Alpha Interferon and Azidothymidine (AZT) in AIDS-Associated Kaposi's Sarcoma

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