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Fludarabine and Monoclonal Antibody Therapy in Treating Patients With Untreated B-cell Chronic Lymphocytic Leukemia

Phase 2
Completed
Conditions
Leukemia
Interventions
Biological: rituximab
Registration Number
NCT00003248
Lead Sponsor
Alliance for Clinical Trials in Oncology
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 monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of fludarabine given with or without monoclonal antibody therapy followed by monoclonal antibody therapy alone in treating patients who have untreated B-cell chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES: I. Determine the response rate and toxicity profile of concurrent and consolidative chimeric anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab) therapy compared to consolidative rituximab therapy in patients with chronic lymphocytic leukemia treated with fludarabine. II. Assess the complete response (CR) rate in patients receiving concurrent therapy with rituximab and fludarabine. III. Assess the frequency of conversion of a partial response (PR) to a CR or stable disease to either PR or CR in patients receiving consolidative therapy with rituximab. IV. Follow the effects of rituximab and fludarabine on the immunologic markers CD4, CD8, IgG, IgA, and IgM. V. Assess the progression-free and overall survival of these patients.

OUTLINE: This is a randomized study. Patients are stratified according to stage (I and II vs III and IV). Patients are assigned to 1 of 2 treatment arms. Arm I consists of fludarabine and chimeric anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab) induction, and arm II consists of fludarabine induction. Arm I: Rituximab is administered IV over 4 hours on day 1, on day 3, and over 1 hour on day 5 of week 1. Subsequent doses are given over 1 hour on day 1 every 4 weeks for a total of 6 courses. Fludarabine IV is administered over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses. Following the sixth course of fludarabine, patients undergo clinical staging and are then observed for an additional 2 months, after which they undergo repeat clinical staging, including bone marrow aspiration. Patients achieving a complete or partial response or stable disease then proceed to consolidation therapy consisting of weekly intravenous infusions of rituximab once weekly for 4 weeks. Arm II (Fludarabine Induction): Patients receive fludarabine IV over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses. Patients then proceed as in arm I. Patients are followed every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 100 patients will be accrued for this study within 12 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
104
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm IrituximabPatients receive fludarabine and chimeric anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab) induction. Rituximab is administered IV over 4 hours on day 1, on day 3, and over 1 hour on day 5 of week 1. Subsequent doses are given over 1 hour on day 1 every 4 weeks for a total of 6 courses. Fludarabine IV is administered over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses. Following the sixth course of fludarabine, patients undergo clinical staging and are then observed for an additional 2 months, after which they undergo repeat clinical staging, including bone marrow aspiration. Patients achieving a complete or partial response or stable disease then proceed to consolidation therapy consisting of weekly intravenous infusions of rituximab once weekly for 4 weeks. Patients are followed every 3 months for 1 year, and then every 6 months thereafter.
Arm IIrituximabPatients receive fludarabine induction. Patients receive fludarabine IV over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses. Patients then proceed as in arm I. Patients are followed every 3 months for 1 year, and then every 6 months thereafter.
Arm IIfludarabine phosphatePatients receive fludarabine induction. Patients receive fludarabine IV over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses. Patients then proceed as in arm I. Patients are followed every 3 months for 1 year, and then every 6 months thereafter.
Arm Ifludarabine phosphatePatients receive fludarabine and chimeric anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab) induction. Rituximab is administered IV over 4 hours on day 1, on day 3, and over 1 hour on day 5 of week 1. Subsequent doses are given over 1 hour on day 1 every 4 weeks for a total of 6 courses. Fludarabine IV is administered over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses. Following the sixth course of fludarabine, patients undergo clinical staging and are then observed for an additional 2 months, after which they undergo repeat clinical staging, including bone marrow aspiration. Patients achieving a complete or partial response or stable disease then proceed to consolidation therapy consisting of weekly intravenous infusions of rituximab once weekly for 4 weeks. Patients are followed every 3 months for 1 year, and then every 6 months thereafter.
Primary Outcome Measures
NameTimeMethod
progression-free survivalUp to 5 years
overall survivalUp to 5 years
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (34)

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

🇺🇸

Baltimore, Maryland, United States

Ellis Fischel Cancer Center - Columbia

🇺🇸

Columbia, Missouri, United States

North Shore University Hospital

🇺🇸

Manhasset, New York, United States

Vermont Cancer Center

🇺🇸

Burlington, Vermont, United States

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

🇺🇸

Syracuse, New York, United States

State University of New York - Upstate Medical University

🇺🇸

Syracuse, New York, United States

University of Massachusetts Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University of Tennessee, Memphis Cancer Center

🇺🇸

Memphis, Tennessee, United States

Barnes-Jewish Hospital

🇺🇸

Saint Louis, Missouri, United States

Mount Sinai Medical Center, NY

🇺🇸

New York, New York, United States

CCOP - Southeast Cancer Control Consortium

🇺🇸

Winston-Salem, North Carolina, United States

Lineberger Comprehensive Cancer Center, UNC

🇺🇸

Chapel Hill, North Carolina, United States

MBCCOP - Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

New York Presbyterian Hospital - Cornell Campus

🇺🇸

New York, New York, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

CCOP - Southern Nevada Cancer Research Foundation

🇺🇸

Las Vegas, Nevada, United States

UCSF Cancer Center and Cancer Research Institute

🇺🇸

San Francisco, California, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Duke Comprehensive Cancer Center

🇺🇸

Durham, North Carolina, United States

CCOP - Christiana Care Health Services

🇺🇸

Wilmington, Delaware, United States

University of California San Diego Cancer Center

🇺🇸

La Jolla, California, United States

CCOP - Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

University of Chicago Cancer Research Center

🇺🇸

Chicago, Illinois, United States

Walter Reed Army Medical Center

🇺🇸

Washington, District of Columbia, United States

University of Illinois at Chicago Health Sciences Center

🇺🇸

Chicago, Illinois, United States

Norris Cotton Cancer Center

🇺🇸

Lebanon, New Hampshire, United States

CCOP - North Shore University Hospital

🇺🇸

Manhasset, New York, United States

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Massachusetts General Hospital Cancer Center

🇺🇸

Boston, Massachusetts, United States

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

🇺🇸

Winston-Salem, North Carolina, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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