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

Study Overview
=================
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.

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

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Biological: filgrastim
* Biological: recombinant interleukin-12
* Drug: etoposide
* Drug: ifosfamide


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br> <br> Biological: recombinant interleukin-12<br> <br> Drug: etoposide<br> <br> Drug: ifosfamide<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AIDS-related peripheral/systemic lymphoma, AIDS-related diffuse large cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related small noncleaved cell lymphoma