RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of fludarabine in treating patients who have chronic lymphocytic leukemia that has not been previously treated.

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

Further Study Details: 

OBJECTIVES:

• Determine the overall response rate (complete and partial) in patients with previously untreated B-cell chronic lymphocytic leukemia treated with oral fludarabine.
• Determine the molecular complete response rate in patients who achieve a clinical or immunophenotypic complete response when treated with this drug.
• Determine the progression-free and treatment-free survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Determine the baseline incidence of defined genetic abnormalities in patients treated with this drug.
• Determine the prognostic and predictive significance of defined genetic abnormalities in patients with respect to response to treatment with this drug.
• Determine the prognostic and predictive significance of immunophenotypic profile of patients with respect to response to treatment with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral fludarabine on days 1-5. Treatment repeats every 28 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission after 6 courses do not receive further study therapy.

Patients are followed at 2 months and then every 4 months for 2 years.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL)
• Previously untreated
• Rai stage I, II, III, or IV
• Requiring systemic therapy
• Persistent lymphocytosis of greater than 5,000/mm
• Morphologically mature lymphocytes
• Monoclonal B-cell population
• CD19/CD5/CD23 positive with kappa or lambda light chain restriction by immunophenotyping
• No other lymphoproliferative disorders including prolymphocytic leukemia, mantle cell lymphoma, progression to aggressive B-cell lymphoma, or Richter's syndrome
• No clinical autoimmune hematologic complication of CLL including Coomb's-positive hemolytic anemia or immune thrombocytopenia
• Positive Coomb's test allowed if no clinical hemolysis

PATIENT CHARACTERISTICS: Age

• 16 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST and/or ALT no greater than 2 times ULN

Renal

• Creatinine no greater than 2 times ULN

Other

• Accessible for treatment and follow-up
• No known HIV infection
• No active bacterial, viral, or fungal infection requiring systemic antibiotics
• No conditions requiring corticosteroid therapy
• No history of other malignancies except for the following:
• Adequately treated nonmelanoma skin cancer
• Curatively treated carcinoma in situ of the cervix
• Other solid tumors curatively treated with no evidence of disease within the past 5 years
• No other major medical illness that would preclude study
• No known hypersensitivity to fludarabine or its components
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent immunotherapy including monoclonal antibody therapy
• No concurrent autologous or allogeneic stem cell or bone marrow transplantation

Chemotherapy

• No other concurrent cytotoxic drugs

Endocrine therapy

• No concurrent corticosteroids except inhaled or topical corticosteroids
• No concurrent corticosteroids for nausea prophylaxis

Radiotherapy

• No prior radiotherapy affecting more than 25% of bone marrow and/or involving the pelvic area
• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior investigational agents
• No other concurrent investigational agents

Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      Providence Health Care - Vancouver, Vancouver,  British Columbia,  V6Z 1Y6,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, New Brunswick
      Moncton Hospital, Moncton,  New Brunswick,  E1C 6ZB,  Canada
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Algoma Reginal Cancer Program at Sault Area Hospital, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Cancer Care Ontario - Windsor Regional Cancer Centre, Windsor,  Ontario,  N8W 2X3,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada
      Durham Regional Cancer Centre at Lakeridge Health Oshawa, Oshawa,  Ontario,  L1G 2B9,  Canada
      Grand River Regional Cancer Centre, Kitchner,  Ontario,  N2G 1G3,  Canada
      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Humber River Regional Hospital - Weston, Weston,  Ontario,  M9N 1N8,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Northeastern Ontario Regional Cancer Centre, Sudbury, Sudbury,  Ontario,  P3E 5J1,  Canada
      Northwestern Ontario Regional Cancer Centre, Thunder Bay, Thunder Bay,  Ontario,  P7A 7T1,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 8L6,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      St. Joseph's Health Centre - Toronto, Toronto,  Ontario,  M6R 1B5,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2L 4MI,  Canada
      CHUS-Hopital Fleurimont, Fleurimont,  Quebec,  J1H 5N4,  Canada
      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada
      Hopital de L'Enfant Jesus, Quebec City,  Quebec,  G1J 1Z4,  Canada
      Hopital du Saint-Sacrement, Quebec, Quebec City,  Quebec,  G1S 4L8,  Canada
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada
France
      Centre Hospitalier Lyon Sud, Pierre-Benite,  69495,  France
      Centre Jean Bernard, Le Mans,  72000,  France

Study chairs or principal investigators

Ralph Melbourne Meyer, MD, FRCPC,  Study Chair,  Margaret and Charles Juravinski Cancer Centre   

Study ID Numbers:  CDR0000257836; CAN-NCIC-CL2; BRLX-304160
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049075
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08