Back to resultsA Study of AZT Plus Human Interferon Alpha in the Treatment of AIDS-Related Kaposi's Sarcoma
Primary Purpose
Sarcoma, Kaposi, HIV Infections
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Interferon alfa-2a
Zidovudine
Interferon alfa-n1
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoma, Kaposi focused on measuring Interferon Alfa-2a, Sarcoma, Kaposi, Dose-Response Relationship, Drug, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, Interferon Type I
Eligibility Criteria
Inclusion Criteria Patient must have a histologically confirmed diagnosis of Kaposi's sarcoma. Positive antibody to HIV confirmed by ELISA or Western blot on the same serum. Exclusion Criteria Active drug or alcohol abuse. Co-existing Condition: Patients with the following complications are excluded: Active opportunistic infections requiring ongoing therapy. Pneumocystis carinii pneumonia (PCP) unless recovered must be off therapy within 90 days prior to study. Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia. Concurrent neoplasms other than basal cell carcinoma of skin. Known sensitivity to polymycin or neomycin. Patients with the following complications are excluded: Active opportunistic infections requiring ongoing therapy. Pneumocystis carinii pneumonia (PCP) unless recovered must be off therapy within 90 days prior to study. Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia. Concurrent neoplasms other than basal cell carcinoma of skin. Known sensitivity to polymycin or neomycin. Prior Medication: Excluded: Any prior zidovudine (AZT) or interferon alpha protocol participation. Excluded within 30 days of study entry: Immunomodulating agents. Other drugs that can cause neutropenia or significant nephrotoxicity, or systemic anti-infectives. Excluded within 90 days of study entry: Antiretroviral agents. Treatment of Pneumocystis carinii pneumonia (PCP). Prior Treatment: Excluded within 30 days of study entry: Radiation therapy.
Sites / Locations
- Mem Sloan - Kettering Cancer Ctr
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00001113
First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT00001113
Brief Title
A Study of AZT Plus Human Interferon Alpha in the Treatment of AIDS-Related Kaposi's Sarcoma
Official Title
A Phase I Study of AZT and Human Interferon Alpha (Recombinant Alpha-2A and Lymphoblastoid) in the Treatment of 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
March 1990 (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 evaluate the safety and toxicity of combination therapy for AIDS-associated Kaposi's sarcoma with zidovudine (AZT) and two kinds of interferon alpha. The two kinds are interferon alpha (IFN-A) and interferon alpha-2A (recombinant) (IFN-A2A). To define the pharmacokinetics of AZT and IFN-A or AZT and IFN-A2A when given in combination. To define the maximum tolerated dose (MTD) of each drug in combination and to define doses to be used in Phase II trial. AZT has been found to be effective against the effects of HIV in vitro (test tube) and both interferons have shown antiviral and antitumor effect on Kaposi's sarcoma. It is reasonable to assume that a synergism and an enhanced antitumor response may be seen with combination therapy. A study to evaluate the safety and effectiveness of AZT in the combination with IFN-A2A is warranted.
Detailed Description
AZT has been found to be effective against the effects of HIV in vitro (test tube) and both interferons have shown antiviral and antitumor effect on Kaposi's sarcoma. It is reasonable to assume that a synergism and an enhanced antitumor response may be seen with combination therapy. A study to evaluate the safety and effectiveness of AZT in the combination with IFN-A2A is warranted.
Patients are randomized to receive IFN-A or IFN-A2A by intramuscular injection and combined with AZT orally daily for 8 weeks. Two cohorts of 4 patients enter each dose level. Patients do not enter into the next dose level until all patients have completed 3 weeks of treatment. AZT escalates only if there is no unacceptable toxicity (grade 2 in = or > 3 patients or > grade 2 in any patients); subsequent increase in IFN-A or IFN-A2A will be permitted, but the AZT dose will remain fixed. The MTD for a given IFN-A or IFN-A2A dose level is defined as grade 3 toxicity for hemoglobin or grade 2 toxicity for other parameters in 3 of the 6 patients. Once the MTD is reached, there will be no further enrollment at higher dose level. Patients are followed every week for vital signs and hematologic studies. Patients tolerating the combination may be continued on therapy for 1 year at the same dose as the end of 8th week.
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-2a, Sarcoma, Kaposi, Dose-Response Relationship, Drug, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, Interferon Type I
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
48 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Interferon alfa-2a
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Interferon alfa-n1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patient must have a histologically confirmed diagnosis of Kaposi's sarcoma.
Positive antibody to HIV confirmed by ELISA or Western blot on the same serum.
Exclusion Criteria
Active drug or alcohol abuse.
Co-existing Condition:
Patients with the following complications are excluded:
Active opportunistic infections requiring ongoing therapy.
Pneumocystis carinii pneumonia (PCP) unless recovered must be off therapy within 90 days prior to study.
Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia.
Concurrent neoplasms other than basal cell carcinoma of skin.
Known sensitivity to polymycin or neomycin.
Patients with the following complications are excluded:
Active opportunistic infections requiring ongoing therapy.
Pneumocystis carinii pneumonia (PCP) unless recovered must be off therapy within 90 days prior to study.
Clinically significant cardiac disease, including a history of myocardial infarction or arrhythmia.
Concurrent neoplasms other than basal cell carcinoma of skin.
Known sensitivity to polymycin or neomycin.
Prior Medication:
Excluded:
Any prior zidovudine (AZT) or interferon alpha protocol participation.
Excluded within 30 days of study entry:
Immunomodulating agents.
Other drugs that can cause neutropenia or significant nephrotoxicity, or systemic anti-infectives.
Excluded within 90 days of study entry:
Antiretroviral agents.
Treatment of Pneumocystis carinii pneumonia (PCP).
Prior Treatment:
Excluded within 30 days of study entry:
Radiation therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Krown S
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
1670585
Citation
Fischl MA, Uttamchandani RB, Resnick L, Agarwal R, Fletcher MA, Patrone-Reese J, Dearmas L, Chidekel J, McCann M, Myers M. A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. J Acquir Immune Defic Syndr (1988). 1991;4(1):1-10.
Results Reference
background
PubMed Identifier
2765664
Citation
Berman E, Duigou-Osterndorf R, Krown SE, Fanucchi MP, Chou J, Hirsch MS, Clarkson BD, Chou TC. Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells. Blood. 1989 Sep;74(4):1281-6.
Results Reference
background
Citation
Krown S, Bundow D, Gansbacher B, Gold J, Flomenberg N, Armstrong D. Interferon (IFN) alpha+ AZT in AIDS-associated Kaposi's sarcoma (KS): final results of a phase I trial. Int Conf AIDS. 1989 Jun 4-9;5:414 (abstract no WBP374)
Results Reference
background
Citation
ICDB/88643799. Krown SE, et al. Interferon-alpha (IFN-alpha) plus zidovudine (ZDV) in AIDS-associated Kaposi's sarcoma (AIDS/KS): an ongoing phase I trial. Proc Annu Meet Am Soc Clin Oncol. 1988 7:A2
Results Reference
background
PubMed Identifier
1971504
Citation
Krown SE, Gold JW, Niedzwiecki D, Bundow D, Flomenberg N, Gansbacher B, Brew BJ. Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990 Jun 1;112(11):812-21. doi: 10.7326/0003-4819-112-11-812. Erratum In: Ann Intern Med 1990 Aug 15;113(4):334.
Results Reference
background
Citation
Krown S, Bhalla R, Niedzwiecki D, Bundow D. Interferon (IFN), beta-2 microglobulin (beta2-m) and neopterin (Neo) in AIDS-associated Kaposi's sarcoma (KS). Int Conf AIDS. 1989 Jun 4-9;5:216 (abstract no ThBO28)
Results Reference
background
PubMed Identifier
1895208
Citation
Krown SE, Niedzwiecki D, Bhalla RB, Flomenberg N, Bundow D, Chapman D. Relationship and prognostic value of endogenous interferon-alpha, beta 2-microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS. J Acquir Immune Defic Syndr (1988). 1991;4(9):871-80.
Results Reference
background
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A Study of AZT Plus Human Interferon Alpha in the Treatment of AIDS-Related Kaposi's Sarcoma
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