RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of fludarabine plus high-dose cyclophosphamide and rituximab in treating patients who have previously untreated chronic lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia	Drug: cyclophosphamide  Drug: filgrastim  Drug: fludarabine  Drug: rituximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response rate in patients with chronic lymphocytic leukemia treated with sequential fludarabine, high dose cyclophosphamide, and rituximab.
• Assess the improvement in response associated with each phase of this therapy in these patients.
• Characterize the toxicity of this sequential therapy in these patients.
• Utilize flow cytometry and polymerase chain reaction as sensitive measures of minimal residual disease in these patients.

OUTLINE: This is an open label study.

Patients receive fludarabine IV once daily for 5 days. Treatment is repeated every 4 weeks for 3 or 6 courses.

Three weeks later, cyclophosphamide is administered intravenously every 2-3 weeks for 3 courses. Filgrastim (G-CSF) is administered on days 2-10. Beginning 4 weeks after the last dose of cyclophosphamide, patients receive rituximab by intravenous infusion once weekly for 4 weeks.

Patient are followed every 3 months until death.

PROJECTED ACCRUAL: This study will accrue 30 patients within 3 years.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically diagnosed previously untreated intermediate or high risk chronic lymphocytic leukemia
• Montserrat "smouldering leukemia" not eligible

PATIENT CHARACTERISTICS: Age:

• 18 to 75

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 4 weeks

Hematopoietic:

• Lymphocyte count at least 5000/mm^3
• Bone marrow lymphocytosis at least 30% of nucleated cells
• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No serious cardiac condition

Other:

• No autoimmune hemolytic anemia
• No autoimmune thrombocytopenia
• No active infections requiring systemic antibiotics
• Not pregnant or nursing
• Fertile women must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic treatment for chronic lymphocytic leukemia
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent prednisone therapy

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Mark Adam Weiss, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000066752; MSKCC-98080; NCI-G98-1483; NCT00003659
Record last reviewed:  February 1999
Last Updated:  December 6, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003659
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08