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

This study has been completed.
Sponsor:
Collaborators:
Schering-Plough
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001114
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012

November 2, 1999
March 28, 2012
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Complete list of historical versions of study NCT00001114 on ClinicalTrials.gov Archive Site
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The Safety and Effectiveness of Interferon Alfa-2B Plus Didanosine in Patients With Kaposi's Sarcoma
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety Study
Primary Purpose: Treatment
  • Sarcoma, Kaposi
  • HIV Infections
  • Drug: Interferon alfa-2b
  • Drug: Didanosine
Not Provided
Krown SE, Li P, Von Roenn JH, Paredes J, Huang J, Testa MA. Efficacy of low-dose interferon with antiretroviral therapy in Kaposi's sarcoma: a randomized phase II AIDS clinical trials group study. J Interferon Cytokine Res. 2002 Mar;22(3):295-303.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
90
March 2000
Not Provided

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.
Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00001114
ACTG 206, 11183
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
  • Schering-Plough
  • Bristol-Myers Squibb
Study Chair: Krown SE
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP