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

July 19, 2016 updated by: Alliance for Clinical Trials in Oncology

A Randomized Phase II Study of Concurrent Fludarabine + Chimeric Anti-CD20 Monoclonal Antibody IDEC-C2B8 (Rituximab) [NSC# 687451] Induction Followed By Rituximab Consolidation In Untreated Patients With B-Cell Chronic Lymphocytic Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

104

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093-0658
        • University of California San Diego Cancer Center
      • San Francisco, California, United States, 94115-0128
        • UCSF Cancer Center and Cancer Research Institute
    • Delaware
      • Wilmington, Delaware, United States, 19899
        • CCOP - Christiana Care Health Services
    • District of Columbia
      • Washington, District of Columbia, United States, 20307-5000
        • Walter Reed Army Medical Center
    • Florida
      • Miami Beach, Florida, United States, 33140
        • CCOP - Mount Sinai Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Cancer Research Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago Health Sciences Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Memorial Medical Center
    • Missouri
      • Columbia, Missouri, United States, 65203
        • Ellis Fischel Cancer Center - Columbia
      • Saint Louis, Missouri, United States, 63110
        • Barnes-Jewish Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198-3330
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • CCOP - Southern Nevada Cancer Research Foundation
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Norris Cotton Cancer Center
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • Manhasset, New York, United States, 11030
        • CCOP - North Shore University Hospital
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10021
        • New York Presbyterian Hospital - Cornell Campus
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center, NY
      • Syracuse, New York, United States, 13210
        • State University of New York - Upstate Medical University
      • Syracuse, New York, United States, 13210
        • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center, UNC
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Winston-Salem, North Carolina, United States, 27104-4241
        • CCOP - Southeast Cancer Control Consortium
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425-0721
        • Medical University of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • University of Tennessee, Memphis Cancer Center
    • Vermont
      • Burlington, Vermont, United States, 05401-3498
        • Vermont Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • MBCCOP - Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: fludarabine phosphate
Biological: rituximab
Experimental: 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.
Drug: fludarabine phosphate
Biological: rituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
overall survival
Time Frame: Up to 5 years
Up to 5 years
progression-free survival
Time Frame: Up to 5 years
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: John C. Byrd, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1998

Primary Completion (Actual)

April 1, 2003

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

September 9, 2004

First Posted (Estimate)

September 10, 2004

Study Record Updates

Last Update Posted (Estimate)

July 20, 2016

Last Update Submitted That Met QC Criteria

July 19, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-9712
  • U01CA062475 (U.S. NIH Grant/Contract)
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CLB-9712
  • CDR0000066128 (Registry Identifier: NCI Physicians Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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