A Phase I/II Study of Recombinant Interleukin-4 in AIDS and Kaposi's Sarcoma

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000769

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

To determine the safety and tolerance of interleukin-4 (IL-4) in patients with AIDS-related Kaposi's sarcoma. To determine the effects of IL-4 on tumor growth in patients with AIDS-related Kaposi's sarcoma.

IL-4 exhibits a variety of beneficial effects on the immune system and is a potent inhibitor of Kaposi's sarcoma cells in vitro.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Kaposi HIV Infections	Drug: Interleukin-4	Phase 1

Detailed Description

IL-4 exhibits a variety of beneficial effects on the immune system and is a potent inhibitor of Kaposi's sarcoma cells in vitro.

Patients are stratified into two groups according to CD4 count (less than 100 cells/mm3 and greater than or equal to 100 cells/mm3) and are enrolled in cohorts of four patients at each of four dose levels of IL-4 per stratum. Within each stratum, if patients at a given dose level have received at least 2 weeks of study therapy and no more than two patients experienced grade 3 or 4 drug-related toxicity, dose escalation in subsequent patients may begin. The MTD is defined as the dose at which 50 percent of patients develop grade 3 or worse toxicity. Patients with CD4 count less than 500 cells/mm3 (per 12/30/94 amendment) must be on antiretroviral therapy during study treatment.

PER AMENDMENT 11/20/95: Group I - enrollment is closed, the objective has been defined. Group II - patients must have CD4 cells greater than or equal to 100/mm3 and less than 500/mm3.

PER AMENDMENT 11/20/95: All patients will receive antiretroviral therapy.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of Recombinant Interleukin-4 in AIDS and Kaposi's Sarcoma

Actual Study Completion Date :

Apr 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Required:

Antiretroviral therapy during study treatment only in patients with CD4 count < 500 cells/mm3 (per 12/30/94 amendment).

Allowed:

G-CSF for a second occurrence of grade 3 or 4 neutropenia (per 12/30/94 amendment).
Nonsteroidal anti-inflammatory agents including acetaminophen for drug-related fevers.
Systemic steroids for no more than 1 week in any 30-day period.
PCP prophylaxis with TMP/SMX, dapsone, or inhaled pentamidine, if patient has a history of PCP or a CD4 count < 250 cells/mm3.

Allowed only in patients with CD4 count < 100 cells/mm3:

Maintenance doses of ganciclovir, pyrimethamine/sulfa and TMP/SMX for stable, well-controlled opportunistic infections.
Non-myelosuppressive treatment IND medications.

Prior Medication: Required: PER AMENDMENT 11/20/95:

Stable dose of antiretroviral therapy required for at least 21 days prior to study entry for all patients. (Changed from - Stable dose of antiretroviral therapy for at least 21 days prior to study entry in patients with CD4 count < 500 cells/mm3 (per 12/30/94 amendment).

Patients must have:

AIDS-related Kaposi's sarcoma.
PER AMENDMENT 11/20/95: CD4 lymphocyte count >= 100 but < 500 cells/mm3. (Changed from
HIV infection.)
PER AMENDMENT 11/20/95: All Patients will receive antiretroviral therapy. (Changed from - Current antiretroviral therapy IF CD4 count < 500 cells/mm3 (per 12/30/94 amendment).)
No active opportunistic infections requiring induction therapy.
Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Other active malignancies (except basal cell carcinoma of the skin and in situ cervical cancer).
Alteration in mental status that may prevent compliance.
Cardiac functional capacity of Class II or worse OR regional wall abnormalities or abnormal ejection fraction on two-dimensional echocardiogram, if performed.

Concurrent Medication:

Excluded:

Chemotherapy, interferons, or immune modulators for Kaposi's sarcoma.
Myelosuppressive agents such as induction doses of ganciclovir, Fansidar (pyrimethamine/sulfadoxine), or any other investigational drugs (with the exception of non-myelosuppressive treatment IND medications in specific patients).
GM-CSF or erythropoietin (except for a second grade 3/4 neutropenia or anemia).
G-CSF.

Patients with the following prior conditions are excluded:

History of myocardial infarction or significant arrhythmias.
History of symptomatic hypoglycemia.

Prior Medication:

Excluded:

Systemic therapy (including chemotherapy, interferons, and immune modulators) for Kaposi's sarcoma within 4 weeks prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA CARE Center CRS	Los Angeles	California	United States	90095
2	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
3	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215