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

Lymphoma Clinical Trial

Official title:

A Randomized Pre-Phase II Trial of Interleukin-2, Interleukin-12, or No Additional Therapy Following Response to Ifosfamide/Etoposide Chemotherapy for Refractory HIV-Associated Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003575
• Other study ID #: NCI-2012-02276
• Secondary ID: AMC-008CDR000006
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: February 7, 2013
• Start date: January 1999

Study information

• Verified date: October 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. primary completion date: April 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim

• recombinant interleukin-12

Drug:
• etoposide

• ifosfamide

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	University Hospital/New Jersey Cancer Center	Newark	New Jersey
United States	San Francisco General Hospital Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,