A Randomized Phase II Trial to Determine the Safety, Tolerance, and Efficacy of Two Doses of Interferon Alfa-2b Combined With Didanosine in Patients With Kaposi's Sarcoma

Inclusion Criteria

Concurrent Medication:

Allowed:

• Chemoprophylaxis for candidiasis and herpes simplex.
• Up to 14 days of metronidazole.
• Recombinant erythropoietin.
• G-CSF (for severe cases of neutropenia).
• Isoniazid for treatment of TB if given in conjunction with pyridoxine.

Required in patients with CD4 counts < 200 cells/mm3:

• Prophylaxis for PCP.

PER AMENDMENT 9/19/96:

• After the first 16 weeks of combined IFN alpha-2b and ddI treatment subjects may at the discretion of the investigator receive any FDA approved antiretroviral drug regimen in addition to or in place of ddI.

Patients must have:

• Positive antibody to HIV.
• Biopsy-proven Kaposi's sarcoma (at least 5 measurable lesions, with at least 1 measurable cutaneous lesion) involving the skin, lymph nodes, oral cavity, or asymptomatic lesions of the GI tract not requiring systemic chemotherapy. Lung involvement with Kaposi's sarcoma excludes.
• Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Concurrent opportunistic infection or B symptoms including unexplained fever, night sweats, weight loss > 10 percent, and diarrhea lasting more than 2 weeks.
• Visceral (non-nodal) Kaposi's sarcoma requiring cytotoxic chemotherapy.
• Severe (> 2+) tumor-associated edema.
• Concurrent neoplasia other than basal cell carcinoma, or anogenital intraepithelial neoplasia.
• Current clinical evidence of peripheral neuropathy (= or > grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not well controlled by anti-seizure medications.
• Significant symptomatic cardiac disease.
• Medical contraindication.

Concurrent Medication:

Excluded:

• Other investigational, antiviral, immunomodulating, or antitumor agents.
• Drugs associated with peripheral neuropathy (other than ddI).

PER AMENDMENT 9/19/96:

• Other antiretroviral agents may not be taken during the first 16 weeks of combined IFN alpha-2b and ddI treatment.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following prior conditions are excluded:

• Opportunistic infection or B symptoms including unexplained fever, night sweats, weight loss > 10 percent, and diarrhea lasting more than 2 weeks.
• Prior grade 3 or 4 toxicity attributed to ddI therapy.
• Prior history of peripheral neuropathy (= or > grade 1), pancreatitis, intractable diarrhea, or active seizure disorder not well controlled by anti-seizure medications.
• History of myocardial infarction or ventricular arrhythmias.

Prior Medication:

Excluded:

• Prior IFN-alpha.
• Corticosteroids, biological response modifiers, cytotoxic chemotherapy, or known neurotoxic drugs (other than ddI or ddC) within 30 days prior to study entry.
• Therapy with antiretroviral drugs (other than ddI) within 7 days prior to study entry.

Prior Treatment:

Excluded:

• Radiation therapy within 30 days prior to study entry.

Risk Behavior:

• Alcohol consumption is strongly discouraged.
• Patients considered to be noncompliant should be excluded.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety