RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Alternating treatment with more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of fludarabine alternating with cyclophosphamide in treating patients who have previously untreated chronic lymphocytic leukemia.

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

Further Study Details: 

OBJECTIVES: I. Determine the rate and duration of complete and partial remissions in patients with previously untreated B-cell chronic lymphocytic leukemia after treatment with alternating courses of fludarabine and cyclophosphamide.

II. Monitor and assess toxicity of this regimen in these patients.

III. Utilize molecular genetic studies and flow cytometry on peripheral blood cells from patients achieving complete remission by conventional criteria.

IV. Apply FISH techniques using probes to chromosomes 12 and 13 as prognostic factors for time to progression and overall survival of these patients.

PROTOCOL OUTLINE: Patients receive alternating courses of fludarabine and cyclophosphamide. Fludarabine is administered IV over 10-30 minutes on days 1-5 of courses 1, 3, and 5. Cyclophosphamide is administered IV over 30-60 minutes on day 1 of courses 2, 4, and 6. Treatment repeats every 4 weeks.

Patients achieving clinical complete remission (CCR) after 6 courses of chemotherapy receive 2 additional courses (one course of each drug).

Patients achieving partial remission after 6 courses of chemotherapy also receive 2 additional courses. If these patients then achieve CCR, they receive another 2 courses.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 22 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL) manifested by all of the following: Threshold peripheral lymphocyte count greater than 5000/mm3; Small to moderate peripheral lymphocytes with no greater than 55% prolymphocytes; Peripheral lymphocyte count less than 15,000/mm3; At least 30% lymphoid cells in bone marrow; Monoclonality of B lymphocytes
• Active disease by at least one of the following criteria: Weight loss of at least 10% within the past 6 months or prolonged fever or night sweats without evidence of infection; Progressive marrow failure (stage III or IV disease) manifested by Hemoglobin less than 11 g/dL (anemia) AND/OR Platelet count less than 100,000/mm3 (thrombocytopenia); Autoimmune anemia and/or thrombocytopenia minimally responsive to corticosteroid therapy; Massive or progressive splenomegaly Massive or progressive lymphadenopathy; Progressive lymphocytosis (not due to the effects of corticosteroids); Marked hypogammaglobulinemia or development of monoclonal protein in the absence of any of the above criteria is not sufficient for eligibility

--Prior/Concurrent Therapy--

• Biologic therapy: Prior interferon allowed
• Chemotherapy: No prior cytotoxic chemotherapy
• Endocrine therapy: See Disease Characteristics; Prior corticosteroids, somatostatin analogues, and tamoxifen allowed
• Radiotherapy: At least 4 weeks since prior radiotherapy
• Surgery: At least 4 weeks since prior major surgery

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); SGOT no greater than 1.5 times ULN (unless due to hemolysis or CLL)
• Renal: Creatinine no greater than 1.5 times ULN
• Cardiovascular: No New York Heart Association class III or IV heart disease; No myocardial infarction in the past month
• Other: No uncontrolled infection; No active infection with HIV (AIDS); No other malignancy within past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix; Not pregnant or nursing; Fertile patients must use effective contraception

Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      CentraCare Clinic, Saint Cloud,  Minnesota,  56303,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
North Dakota
      Altru Health Systems, Grand Forks,  North Dakota,  58201,  United States
      Quain & Ramstad Clinic, P.C., Bismarck,  North Dakota,  58501,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57105-1080,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States

Study chairs or principal investigators

Thomas E. Witzig,  Study Chair,  North Central Cancer Treatment Group   

Study ID Numbers:  CDR0000066985; NCCTG-978151
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003829
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08