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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: ifosfamide

Drug: etoposide

Biological: recombinant interleukin-12

Biological: filgrastim

Study type

Interventional

Funder types

NIH

Identifiers

NCT00003575

NCI-2012-02276

CDR0000066642 (Registry Identifier)

AMC-008

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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