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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003575
First received: November 1, 1999
Last updated: February 7, 2013
Last verified: October 2002
  Purpose

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 Intervention Phase
Lymphoma
Biological: filgrastim
Biological: recombinant interleukin-12
Drug: etoposide
Drug: ifosfamide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 40
Study Start Date: January 1999
Primary Completion Date: April 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003575

Locations
United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033-0800
San Francisco General Hospital Medical Center
San Francisco, California, United States, 94110
United States, Florida
Sylvester Cancer Center, University of Miami
Miami, Florida, United States, 33136
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114-2617
United States, New Jersey
University Hospital/New Jersey Cancer Center
Newark, New Jersey, United States, 07103
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
United States, Ohio
Arthur G. James Cancer Hospital - Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Study Chair: Lawrence D. Kaplan, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003575     History of Changes
Other Study ID Numbers: NCI-2012-02276, AMC-008, CDR0000066642
Study First Received: November 1, 1999
Last Updated: February 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
AIDS-related peripheral/systemic lymphoma
AIDS-related diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related small noncleaved cell lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide
Etoposide phosphate
Isophosphamide mustard
Ifosfamide
Interleukin-12
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014