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.

Condition	Treatment or Intervention	Phase
stage II chronic lymphocytic leukemia B-cell Chronic Lymphocytic Leukemia stage IV chronic lymphocytic leukemia stage I chronic lymphocytic leukemia stage III chronic lymphocytic leukemia	Drug: fludarabine  Drug: rituximab	Phase II

Further Study Details: 

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.

PROTOCOL 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 intravenously over 4-8 hours on days 1 and 4 of week 1, then every 4 weeks for a total of 7 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 over 4-8 hours 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 70 patients will be accrued for this study within 12 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--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

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

Study chairs or principal investigators

John C. Byrd,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000066128; CLB-9712
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003248
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08