Combination Chemotherapy and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

Sponsor

Hoag Memorial Hospital Presbyterian (Other)

Overall Status

Completed

CT.gov ID

NCT00049413

Collaborator

Cancer Biotherapy Research Group (Other)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining pentostatin and cyclophosphamide with rituximab in treating patients who have chronic lymphocytic leukemia or lymphocytic lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: pentostatin	Phase 2

Detailed Description

OBJECTIVES:

Determine the efficacy of pentostatin, cyclophosphamide, and rituximab, in terms of response rate, time to treatment failure, time to disease progression, durability of response, and overall survival, in patients with B-cell chronic lymphocytic leukemia or small B-cell lymphocytic lymphoma.
Determine the safety of this regimen, in terms of acute, subacute, and chronic toxicity, in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (no prior chemotherapy for chronic lymphocytic leukemia vs prior purine analog-based therapy [fludarabine or cladribine] but no alkylator therapy vs prior alkylator-based therapy [chlorambucil or cyclophosphamide] but no prior purine analog therapy vs prior therapy with alkylators and purine analogs, but not as combination therapy).

First course: Patients receive rituximab IV over 1-4 hours on days 1-3 and pentostatin IV over 10-30 minutes and cyclophosphamide IV over 30-60 minutes on day 1.
All subsequent courses: Patients receive rituximab IV over 60 minutes, pentostatin IV over 10-30 minutes, and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 160-240 patients (40-60 per stratum) will be accrued for this study.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pentostatin, Cyclophosphamide And Rituximab (PCR) For B-Cell Chronic Lymphocytic Leukemia (CLL) And Small B-Cell Lymphocytic Lymphoma (SLL): Four Phase II Trials With Patient Stratification Based On Prior Therapy

Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Dec 1, 2004

Actual Study Completion Date :

Dec 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small B-cell lymphocytic lymphoma (SLL) with the following:
Lymph node biopsy interpreted as SLL or consistent with CLL or all of the following:
Peripheral lymphocyte count greater than 5,000/mm^3 with small to moderate peripheral lymphocytes and no more than 55% prolymphocytes
Bone marrow aspirate containing at least 30% lymphoid cells
Immunophenotypic evaluation of peripheral blood lymphocytes demonstrating monoclonality of B lymphocytes with all of the following:
CD19 or CD20 coexpressed with CD5 antigen in the absence of other pan-T- cell markers (e.g., CD2 or CD3)
Expression of CD23 on CLL cells or Dim B-cell expression of kappa or lambda light chains
Measurable disease with any of the following:
1 or more lymph nodes at least 1.5 cm by CT scan
Splenomegaly by CT scan
Peripheral lymphocyte count greater than 5,000/mm3 with coexpression of CD5 and B-cell markers
Bone marrow aspirate with at least 30% lymphoid cells
No mantle cell lymphoma

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

At least 2 years

Hematopoietic

See Disease Characteristics
No immune thrombocytopenia
No hemolytic anemia

Hepatic

Bilirubin no greater than 3 times upper limit of normal (ULN)
SGOT no greater than 3 times ULN (unless due to hemolysis or CLL)
No hepatitis

Renal

Creatinine no greater than 1.5 times ULN

Cardiovascular

No cardiac dysfunction
No New York Heart Association class III or IV heart disease
No myocardial infarction within the past month

Other

HIV negative
No active acute or chronic infection
No immunosuppressive diseases
No autoimmune disorder
No secondary malignancy that is projected to limit life expectancy
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Chemotherapy
No prior rituximab
At least 4 weeks since prior biologic therapy

Chemotherapy

At least 4 weeks since prior chemotherapy
No prior combination chemotherapy and rituximab or other antibody therapy
No prior combination chemotherapy comprising an alkylating agent and a purine nucleoside analog (i.e., cyclophosphamide or chlorambucil in combination with fludarabine, cladribine, or pentostatin)
No prior pentostatin

Endocrine therapy