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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003575

Collaborator

(none)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Biological: recombinant interleukin-12 Drug: etoposide Drug: ifosfamide	Phase 2

Detailed Description

OBJECTIVES:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 1999

Actual Primary Completion Date :

Apr 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: filgrastim Biological: recombinant interleukin-12 Drug: etoposide Drug: ifosfamide

Arm

Intervention/Treatment

Experimental: Arm I

Biological: filgrastim

Biological: recombinant interleukin-12

Drug: etoposide

Drug: ifosfamide

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
2	San Francisco General Hospital Medical Center	San Francisco	California	United States	94110
3	Sylvester Cancer Center, University of Miami	Miami	Florida	United States	33136
4	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois	United States	60611
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114-2617
6	University Hospital/New Jersey Cancer Center	Newark	New Jersey	United States	07103
7	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
8	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
9	Mount Sinai School of Medicine	New York	New York	United States	10029
10	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210