Rituximab Plus Interleukin-2 in Treating Patients With Hematologic Cancer

NCT ID: NCT00010192

Last Updated: 2013-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-12-31

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (rituximab and aldesleukin)

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.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

aldesleukin

Intervention Type: BIOLOGICAL

Given SC

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

rituximab

Given IV

Intervention Type: BIOLOGICAL

aldesleukin

Given SC

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; IL-2; Proleukin; recombinant human interleukin-2; recombinant interleukin-2; pharmacological studies

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierluigi Porcu

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

0037

Identifier Type: -

Identifier Source: secondary_id

CDR0000068454

Identifier Type: -

Identifier Source: secondary_id

OSU-0037

Identifier Type: -

Identifier Source: secondary_id

NCI-130

Identifier Type: -

Identifier Source: secondary_id

OSU-00H0223

Identifier Type: -

Identifier Source: secondary_id

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01404

Identifier Type: -

Identifier Source: org_study_id