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

NCT ID: NCT00001114

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2000-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sarcoma, Kaposi HIV Infections

Keywords

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Sarcoma, Kaposi Didanosine Drug Interactions Acquired Immunodeficiency Syndrome Interferon-alpha

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Interferon alfa-2b

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Schering-Plough

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Krown SE

Role: STUDY_CHAIR

Locations

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Stanford CRS

Palo Alto, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

Puerto Rico-AIDS CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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. doi: 10.1089/107999002753675712.

Reference Type BACKGROUND
PMID: 12034036 (View on PubMed)

Other Identifiers

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11183

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 206

Identifier Type: -

Identifier Source: org_study_id