The Safety and Effectiveness of Interferon Alfa-2B Plus Didanosine in Patients With Kaposi's Sarcoma

• Status: Completed
• Trial end date: 2000-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary: To evaluate the safety, toxicity, and antitumor activity of two doses of interferon alfa-2b (IFN-alpha) combined with a fixed dose of didanosine (ddI) in patients with Kaposi's sarcoma associated with HIV infection.

Secondary: To evaluate the effects of combined IFN-alpha and ddI treatment on HIV expression and markers of immune function.

Previous studies have shown that IFN-alpha can induce regression of Kaposi's sarcoma and suppression of HIV in some patients. Although various trials using IFN-alpha in combination with the nucleoside analogue zidovudine have demonstrated a high degree of antitumor activity and evidence of HIV suppression, the overlapping toxicity (primarily neutropenia) of these two agents has proven dose-limiting. The toxicity profile of ddI suggests that this drug may be better tolerated than zidovudine when combined with IFN-alpha.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Schering-Plough
• Treatments: Didanosine; Interferon alpha-2; Interferon-alpha; Interferons

Criteria

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.