Interleukin-12 Plus Rituximab in Treating Patients With Non-Hodgkin's Lymphoma
Interleukin-12 Plus Rituximab in Treating Patients With Non-Hodgkin's Lymphoma
RATIONALE: Interleukin-12 may stimulate a person's white blood cells to kill lymphoma cells.
 Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or
 deliver cancer-killing substances to them without harming normal cells.

 PURPOSE: Phase I trial to study the effectiveness of interleukin-12 plus rituximab in
 treating patients who have non-Hodgkin's lymphoma.
OBJECTIVES: I. Determine the optimal immunological dose of interleukin-12 and rituximab when
 administered in combination in patients with non-Hodgkin's lymphoma. II. Determine the
 toxicities associated with this regimen in this patient population. III. Assess the
 pharmacodynamics of this regimen in these patients. IV. Document observed clinical response
 to this regimen in these patients.

 OUTLINE: This is a dose escalation study of interleukin-12. Patients receive rituximab IV on
 days 1, 8, 15, and 22. The first cohort of patients receives interleukin-12 SC twice weekly
 beginning on day 29. Subsequent cohorts receive interleukin-12 SC twice weekly beginning on
 day 16. Patients with stable or responding disease may continue treatment with interleukin-12
 twice weekly for up to 24 weeks or until disease progression. Cohorts of 6-9 patients receive
 escalating doses of interleukin-12 until the optimal immunological dose is determined. The
 optimal immunological dose is defined as the dose preceding that at which 2 of 6 or 2 of 9
 patients experience dose limiting toxicities or the dose at which there is a maximal increase
 in gamma interferon, inducible protein-10 (IP-10) and immune cell infiltration into the
 lymphoma (whichever dose is lower). Following initial dose escalation, 2 additional cohorts
 of 6 patients receive a fixed dose of interleukin-12 SC twice weekly beginning on day 2.
 Patients are followed every 3 months for the first year, and then every 6 months for the next
 4 years or until disease progression.

 PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 12-13
 months.
DISEASE CHARACTERISTICS: Histologically confirmed CD20+ B-cell non-Hodgkin's lymphoma No
 relapsed intermediate or high grade disease eligible for bone marrow or stem cell
 transplant Intermediate or high grade disease must have received a prior anthracycline
 containing regimen Low grade disease (with or without prior therapy) felt to be incurable
 with standard therapy allowed No CNS involvement by 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 and over Performance status: ECOG 0-1 Life expectancy: At
 least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
 at least 75,000/mm3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no greater than 3 times
 upper limit of normal (ULN) AST/ALT less than 3 times ULN Renal: Creatinine no greater than
 2 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease No
 history of angina Other: Not pregnant or nursing Negative pregnancy test Fertile patients
 must use effective contraception HIV negative No uncontrolled infection No autoimmune
 related phenomena No peptic ulcer disease

 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 12 months since prior rituximab No
 prior interleukin-12 No other concurrent immunotherapy Chemotherapy: See Disease
 Characteristics No prior fludarabine or 2-chlorodeoxyadenosine unless CD4 count normal
 Recovered from prior chemotherapy No concurrent chemotherapy Endocrine therapy: No
 concurrent steroid therapy Radiotherapy: No concurrent radiotherapy Surgery: Not specified