Rituximab Plus Interleukin-2 in Treating Patients With Hematologic Cancer

A Phase I Trial Of Rituximab And Interleukin-2

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-2 may stimulate a person's white blood cells to kill cancer cells. Combining rituximab with interleukin-2 may kill more cancer cells. Phase I trial to study the effectiveness of rituximab plus interleukin-2 in treating patients who have hematologic cancer.

OBJECTIVES: Determine the dose-limiting toxicity of rituximab followed by low-dose and intermediate-dose pulse interleukin-2 (IL-2) in patients with CD20-positive B-cell lymphoid malignancy.

Determine the maximum tolerated dose of intermediate-dose pulse IL-2 in this patient population.

Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of intermediate-dose pulse aldesleukin.

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients then receive low-dose aldesleukin subcutaneously (SC) on days 29-39, 43-53, 57-67, and 71-81, and intermediate-dose aldesleukin SC on days 40-42, 54-56, 68-70, and 82-84. Cohorts of 3-6 patients receive escalating doses of intermediate-dose pulse aldesleukin until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 1 year.

Inclusion Criteria:

• Histologically or immunophenotypically proven CD20-positive B-cell lymphoproliferative disorder

  • Recurrent or progressive low-grade B-cell lymphoma with at least one prior chemotherapy regimen (may have included monoclonal antibody)
  • Relapsed intermediate-grade or high-grade B-cell lymphoma or B-lineage acute lymphoblastic leukemia and patient not a candidate for, refused, or failed prior hematopoietic stem cell transplantation

• No chronic lymphocytic leukemia or lymphoma with more than 5,000/mm3circulating lymphoma cells

• Measurable or evaluable disease

• Must have failed standard curative therapy

• No CNS or leptomeningeal metastasis

• Performance status - Karnofsky 70-100%

• Performance status - ECOG 0-1

• At least 4 months

• Absolute neutrophil count at least 1,000/mm^3

• Hemoglobin at least 10 g/dL (transfusion allowed)

• Platelet count at least 50,000/mm^3

• AST no greater than upper limit of normal (ULN)

• Bilirubin no greater than 1.5 times ULN

• Hepatitis B surface antigen negative

• Creatinine no greater than ULN

• No prior unstable coronary artery disease

• No New York Heart Association class III or IV congestive heart failure

• DLCO and FEV1 at least 50% of predicted

• HIV negative

• No other concurrent malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix

• No infection requiring IV antibiotic therapy within the past 4 weeks

• No other major illness that would preclude study

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• See Disease Characteristics

• Prior antibody therapy allowed

• Prior interleukin-2 or interferon alfa allowed

• See Disease Characteristics

• At least 4 weeks since prior chemotherapy

• At least 4 weeks since prior systemic corticosteroids

• At least 4 weeks since prior radiotherapy

• At least 4 weeks since prior surgery