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.

Condition	Treatment or Intervention	Phase
Sarcoma, Kaposi HIV Infections	Drug: Interferon alfa-2b  Drug: Didanosine	Phase II

Further Study Details: 

Expected Total Enrollment:  90

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.

Up to 90 patients are randomized to receive either low or high doses of IFN-alpha (1 or 10 million Units/day) in combination with a fixed dose of ddI. Fourteen patients are initially entered at each dose level. If no objective antitumor responses are observed among the first 14 patients at a given dose, no further patients are entered on that treatment arm. If one or more antitumor responses are seen at a given dose, up to 45 patients may be entered on that treatment arm. Patients must complete at least 4 weeks of study therapy to be considered evaluable for tumor response. Treatment is continued until tumor progression or unacceptable toxicity occurs. PER AMENDMENT 9/19/96: NOTE - After 16 weeks of treatment subjects may receive any FDA approved antiretroviral drug regimen in addition to or in place of ddI.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

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.

California
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
      Denver Dept of Health and Hosps, Denver,  Colorado,  80262,  United States
      Kaiser Permanente Franklin Med Ctr, Denver,  Colorado,  80262,  United States
      Rose Med Ctr, Denver,  Colorado,  80262,  United States
Connecticut
      Yale Univ / New Haven, New Haven,  Connecticut,  065102483,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Massachusetts
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
New York
      SUNY / State Univ of New York, Syracuse,  New York,  13210,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Adirondack Med Ctr at Saranac Lake, Albany,  New York,  122083479,  United States
      Mid - Hudson Care Ctr, Albany,  New York,  122083479,  United States
      Albany Med College / Division of HIV Medicine A158, Albany,  New York,  122083479,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
Ohio
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Krown SE,  Study Chair

Study ID Numbers:  ACTG 206
Record last reviewed:  February 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001114
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08