Rituximab Plus Interleukin-2 in Treating Patients With Hematologic Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Stage IV Small Lymphocytic Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Stage III Grade 3 Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Recurrent Mantle Cell Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Recurrent Adult Burkitt Lymphoma; Stage III Marginal Zone Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Grade 1 Follicular Lymphoma

Treatments: Biological: rituximab; Other: laboratory biomarker analysis; Other: pharmacological study; Biological: aldesleukin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00010192

OSU-0037

OSU-00H0223

CDR0000068454

U01CA076576 (U.S. NIH Grant/Contract)

NCI-2012-01404

0037

NCI-130

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Treatment (rituximab and aldesleukin)

Experimental group

Description:

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients then receive low-dose aldesleukin 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.

Treatment:

Biological: aldesleukin

Other: pharmacological study

Other: laboratory biomarker analysis

Biological: rituximab