Randomized Phase II Study Of Interleukin-12 In Combination With Rituximab In Patients With Non-Hodgkin's Lymphoma
Randomized Phase II Study Of Interleukin-12 In Combination With Rituximab In Patients With Non-Hodgkin's Lymphoma
Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Interleukin-12 may kill cancer cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Combining rituximab with interleukin-12 may kill more cancer cells. This randomized phase II trial is comparing how well giving rituximab together with two different schedules of interleukin-12 works in treating patients with B-cell non-Hodgkin lymphoma.
OBJECTIVES:
I. Compare the objective response in patients with B-cell non-Hodgkin's lymphoma treated with rituximab and 2 different schedules of interleukin-12*.
II. Compare the toxic effects of these regimens in these patients. III. Determine the objective response rate in patients with mantle cell lymphoma treated with these regimens.
IV. Determine the overall and progression-free survival of patients treated with these regimens.
V, Compare the quality of life of patients treated with these regimens. NOTE: *Interleukin-12 will no longer be available after 6/30/05.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (mantle cell lymphoma vs other [closed to accrual as of 3/10/04]) and International Prognostic Factor Index (low and low-intermediate risk [closed to accrual as of 3/10/04] vs high-intermediate and high risk). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive rituximab IV on days 1, 8, 15, and 22. Patients receive interleukin-12* subcutaneously (SC) twice weekly beginning on day 2 and continuing until disease progression.
ARM II (closed to accrual as of 11/14/03): Patients receive rituximab as in arm I. Patients are evaluated at week 12. Patients with stable or progressive disease receive interleukin-12* SC twice weekly until disease progression or for 24 weeks. Patients with a complete or partial response after rituximab are monitored until disease progression and then begin interleukin-12 SC twice weekly until further disease progression.
NOTE: *Interleukin-12 will no longer be available after 06/30/05. Patients proceed to follow-up as outlined below.
Quality of life is assessed at baseline and at 3 and 6 months.
Patients are followed every 3 months for 1 year and then every 6 months for up to 4 years.
PROJECTED ACCRUAL: A total of 90 patients (45 per treatment arm [arm II closed to accrual as of 11/14/03]) will be accrued for this study within 3 years.
Inclusion Criteria:
Histologically confirmed CD20-positive B-cell non-Hodgkin's lymphoma
Previously treated low-grade lymphoma considered incurable with standard therapy
Previously treated mantle cell lymphoma allowed
Meets one of the following criteria for measurable disease:
No CNS involvement by lymphoma
Performance status - ECOG 0-1
At least 12 weeks
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 75,000/mm^3
Hemoglobin ≥ 8 g/dL
Bilirubin ≤ 3 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Alkaline phosphatase ≤ 3 times ULN
Creatinine ≤ 2 times ULN
No New York Heart Association class III or IV heart disease
No history of angina
No uncontrolled peptic ulcer disease
No uncontrolled infection
No other active malignancy
No autoimmune-related phenomena (e.g., antinuclear antibody less than 2 times ULN, rheumatoid factor less than 2 times ULN, and negative direct Coombs)
HIV negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Prior stem cell transplantation allowed
More than 12 months since prior rituximab
No prior interleukin-12
No other concurrent immunotherapy
Recovered from prior chemotherapy
No concurrent chemotherapy
No concurrent steroid therapy
No concurrent radiotherapy
Any number of prior therapies allowed