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
18 Years
N/A
Both
Leukemia
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
John C. Byrd, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Ohio State University Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000066128
NCT ID:
NCT00003248
Start Date:
March 1998
Completion Date:
June 2010
Related Keywords:
- Leukemia
- stage I chronic lymphocytic leukemia
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- B-cell chronic lymphocytic leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
| University of Massachusetts Memorial Medical Center | Worcester, Massachusetts 01655 |
| Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina 27599-7295 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Comprehensive Cancer Center of Wake Forest University Baptist Medical Center | Winston-Salem, North Carolina 27157-1082 |
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| Rhode Island Hospital | Providence, Rhode Island 02903 |
| Vermont Cancer Center | Burlington, Vermont 05401-3498 |
| CCOP - Southern Nevada Cancer Research Foundation | Las Vegas, Nevada 89106 |
| University of California San Diego Cancer Center | La Jolla, California 92093-0658 |
| UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida 33140 |
| Marlene & Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201 |
| Ellis Fischel Cancer Center - Columbia | Columbia, Missouri 65203 |
| Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
| CCOP - North Shore University Hospital | Manhasset, New York 11030 |
| State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| CCOP - Southeast Cancer Control Consortium | Winston-Salem, North Carolina 27104-4241 |
| University of Tennessee, Memphis Cancer Center | Memphis, Tennessee 38103 |
| MBCCOP - Massey Cancer Center | Richmond, Virginia 23298-0037 |
| Mount Sinai Medical Center, NY | New York, New York 10029 |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| New York Presbyterian Hospital - Cornell Campus | New York, New York 10021 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| North Shore University Hospital | Manhasset, New York 11030 |
| CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. | Syracuse, New York 13217 |
| University of Illinois at Chicago Health Sciences Center | Chicago, Illinois 60612 |
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
