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

NCT ID: NCT00003248

Last Updated: 2016-07-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-03-31

Study Completion Date

2010-06-30

Brief Summary

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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

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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.

Conditions

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Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

Patients 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.

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

fludarabine phosphate

Intervention Type DRUG

Arm II

Patients 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.

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

fludarabine phosphate

Intervention Type DRUG

Interventions

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rituximab

Intervention Type BIOLOGICAL

fludarabine phosphate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven B-cell chronic lymphocytic leukemia Stage I or II with evidence of active disease as defined by: Massive or progressive splenomegaly and/or lymphadenopathy Weight loss of greater than 10% within 6 months CALGB grade 2 or 3 fatigue Fevers of greater than 100.5 C or night sweats for over 2 weeks and no evidence of infection Progressive lymphocytosis Stage III or IV Patient registration on CALGB 9665 required

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: CALGB 0-3 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Creatinine no greater than 1.5 times upper limit of normal Other: No medical condition requiring chronic use of oral corticosteroids Direct antiglobulin test or direct Coombs test negative Not pregnant Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY: Biologic: No prior biologic therapy for disease No concurrent erythropoietin Chemotherapy: No concurrent chemotherapy No prior chemotherapy for disease Endocrine: No concurrent chronic oral corticosteroids No prior corticosteroids for autoimmune complications developing since diagnosis No concurrent hormone therapy for disease related conditions No concurrent dexamethasone or other corticosteroid-based antiemetics Radiotherapy: No concurrent palliative radiotherapy Surgery: Not specified Other: No prophylactic therapy for viral, bacterial, or fungal infections
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John C. Byrd, MD

Role: STUDY_CHAIR

Ohio State University Comprehensive Cancer Center

Locations

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University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

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

Syracuse, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Morrison VA, Peterson BL, Rai KR, et al.: Alemtuzumab increases serious infections in patients with previously untreated chronic lymphocytic leukemia (CLL) receiving fludarabine-based therapy: a comparative analysis of 3 Cancer and Leukemia Group B studies (CALGB 9011, 9712, 19901). [Abstract] Blood 110 (11): A-756, 2007.

Reference Type BACKGROUND

Byrd JC, Rai K, Peterson BL, Appelbaum FR, Morrison VA, Kolitz JE, Shepherd L, Hines JD, Schiffer CA, Larson RA. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005 Jan 1;105(1):49-53. doi: 10.1182/blood-2004-03-0796. Epub 2004 May 11.

Reference Type BACKGROUND
PMID: 15138165 (View on PubMed)

Woyach JA, Ruppert AS, Heerema NA, et al.: Treatment with fludarabine and rituximab produces extended overall survival (OS) and progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) without increased risk of second malignancy: long-term follow up of CALGB study 9712. [Abstract] Blood 114 (22): A-539, 2009.

Reference Type RESULT

Byrd JC, Gribben JG, Peterson BL, Grever MR, Lozanski G, Lucas DM, Lampson B, Larson RA, Caligiuri MA, Heerema NA. Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol. 2006 Jan 20;24(3):437-43. doi: 10.1200/JCO.2005.03.1021. Epub 2005 Dec 12.

Reference Type RESULT
PMID: 16344317 (View on PubMed)

Byrd JC, Peterson BL, Morrison VA, Park K, Jacobson R, Hoke E, Vardiman JW, Rai K, Schiffer CA, Larson RA. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003 Jan 1;101(1):6-14. doi: 10.1182/blood-2002-04-1258. Epub 2002 Jul 5.

Reference Type RESULT
PMID: 12393429 (View on PubMed)

Morrison VA, Byrd JC, Peterson BL, et al.: Adding Rituximab to Fludarabine therapy for patients with untreated chronic lymphocytic leukemia (CLL) does not Increase the risk of infection: Cancer and Leukemia Group B (CALGB) study 9712. [Abstract] Blood 102 (11 Pt 1): A-1606, 2003.

Reference Type RESULT

Byrd JC, Peterson BL, Park K, et al.: Concurrent Rituximab and Fludarabine has a higher complete response rate than sequential treatment in untreated chronic lymphocytic leukemia (CLL) patients: results from CALGB 9712. [Abstract] Blood 98 (11 Pt 1): A-3212, 2001.

Reference Type RESULT

Byrd JC, Peterson B, Park K, et al.: Rituximab added to Fludarabine improves response in previously untreated chronic lymphocytic leukemia: preliminary results from CALGB 9712. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1116, 2001.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062475

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CLB-9712

Identifier Type: -

Identifier Source: secondary_id

CDR0000066128

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-9712

Identifier Type: -

Identifier Source: org_study_id

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