Interleukin-12 Following Chemotherapy in Treating Patients With Refractory HIV-Associated Non-Hodgkin's Lymphoma

NCT ID: NCT00003575

Last Updated: 2013-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-01-31

Brief Summary

Phase II trial to compare the effectiveness of interleukin-12 following chemotherapy in treating patients who have refractory HIV-associated non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person' white blood cells to kill cancer cells.

Detailed Description

OBJECTIVES:

I. Determine the efficacy of interleukin-12 (IL-12) by evaluating its effect on remission duration after response to second line chemotherapy with ifosfamide and etoposide in patients with HIV-associated non-Hodgkin's lymphoma.

II. Determine the safety of IL-12 when administered as maintenance therapy in these patients.

III. Evaluate overall survival of this patient population. IV. Evaluate serum and tissue cytokine levels in these patients. V. Evaluate the effect of IL-12 on HIV viral load and on functional T-cell assays in these patients.

VI. Evaluate the effect of IL-12 on Epstein-Barr Virus (EBV) viral load in these patients.

OUTLINE: This is an open label study.

All patients receive ifosfamide IV by continuous infusion for 2 days, etoposide IV over 2 hours daily on days 1 and 2, and filgrastim (G-CSF) subcutaneously (SC) daily on days 4-13. Courses are repeated every 21 days. Patients who have complete or partial remission after a minimum of 4 courses of chemotherapy receive maintenance therapy consisting of interleukin-12 SC twice weekly beginning on day 28 of the final chemotherapy course and continuing for 6 months or until disease progression. All patients also receive combination antiretroviral therapy during study.

Patients are followed every month for one year, then every 2 months thereafter.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

All patients receive ifosfamide IV by continuous infusion for 2 days, etoposide IV over 2 hours daily on days 1 and 2, and filgrastim (G-CSF) subcutaneously (SC) daily on days 4-13. Courses are repeated every 21 days. Patients who have complete or partial remission after a minimum of 4 courses of chemotherapy receive maintenance therapy consisting of interleukin-12 SC twice weekly beginning on day 28 of the final chemotherapy course and continuing for 6 months or until disease progression. All patients also receive combination antiretroviral therapy during study.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

Interventions

filgrastim

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• HIV-infected patients with histologically or cytologically proven intermediate grade large cell lymphoma; high grade large cell immunoblastic lymphoma; or high grade small noncleaved cell lymphoma who have either failed to respond to or relapsed following first line combination chemotherapy
• Bidimensionally measurable disease
• No CNS lymphoma (parenchymal brain or spinal cord tumor)
• No meningeal lymphoma
• A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

• Age: 18 to 70
• Performance status: Karnofsky 60-100%
• Absolute neutrophil count at least 1,000/mm3
• Platelet count greater than 75,000/mm3
• Hematologic criteria not applicable if abnormal functions are attributable to lymphomatous infiltration of bone marrow or liver
• Bilirubin less than 2.0 mg/dL, except in patients receiving indinavir who have isolated hyperbilirubinemia
• Transaminases less than 5 times upper limit of normal
• Hepatic criteria not applicable if abnormal functions are attributable to lymphomatous infiltration of bone marrow or liver
• Creatinine clearance greater than 60 mL/min
• No other prior or concurrent malignancy except carcinoma in situ of the cervix or nonmetastatic nonmelanomatous skin cancer
• No acute active opportunistic infection requiring antibiotic treatment Patients with Mycobacterium avium complex allowed
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• At least 2 weeks since prior immunomodulating agents
• Concurrent filgrastim (G-CSF) allowed
• Concurrent epoetin alfa allowed
• Concurrent antibiotics may be given if clinically indicated during study
• No more than 2 prior standard treatment regimens for non-Hodgkin's lymphoma
• No concurrent systemic corticosteroids
• Concurrent topical and/or oral antifungal agents permitted

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lawrence D. Kaplan, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

San Francisco General Hospital Medical Center

San Francisco, California, United States

Sylvester Cancer Center, University of Miami

Miami, Florida, United States

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University Hospital/New Jersey Cancer Center

Newark, New Jersey, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Countries

United States

Other Identifiers

AMC-008

Identifier Type: -

Identifier Source: secondary_id

CDR0000066642

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02276

Identifier Type: -

Identifier Source: org_study_id