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

PURPOSE: Phase II trial to study the effectiveness of remission induction therapy using cladribine combined with rituximab followed by rituximab and stem cell mobilization in treating patients who have chronic lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
B-cell Chronic Lymphocytic Leukemia refractory chronic lymphocytic leukemia stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia stage I chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia	Drug: cladribine  Drug: cyclophosphamide  Drug: doxorubicin  Drug: filgrastim  Drug: prednisone  Drug: rituximab  Drug: vincristine  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: Primary

• Determine the efficacy and tolerability of cladribine and rituximab as remission induction therapy in patients with chronic lymphocytic leukemia.
• Determine the complete remission rate in patients treated with this regimen.

Secondary

• Determine the very good partial remission rate and nodular partial remission rate in patients treated with this regimen.
• Determine the toxicity of this regimen, in terms of hemotoxicity and infection rate, in these patients.
• Determine the efficacy of in vivo purging with rituximab measured by immunophenotyping in these patients.
• Determine the feasibility of stem cell harvest in these patients after treatment with this induction therapy regimen and in vivo purging with rituximab.

OUTLINE: This is a multicenter study.

• Patients receive cladribine subcutaneously (SC) on days 1-5. During courses 2-4, patients also receive rituximab IV on day 1. Treatment repeats every 28 days for up to 4 courses in the absence of unacceptable toxicity. If unacceptable toxicity persists, patients receive rituximab alone. Patients not achieving a complete remission (CR), very good partial remission (VGPR), or nodular partial remission (NPR) receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 4 courses or until patients achieve a CR, VGPR, or NPR.

Patients achieving a CR, VGPR, or NPR proceed to stem cell mobilization and in vivo purging.

• Stem cell mobilization and in vivo purging: Beginning 8-10 weeks after the first day of the last course of remission induction or CHOP, patients receive rituximab IV on days 1 and 8, cyclophosphamide IV over 4 hours on day 2, and filgrastim (G-CSF) SC daily beginning on day 4 and continuing until the last day of apheresis. Patients undergo apheresis on days 11-14.

PROJECTED ACCRUAL: A total of 17-41 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL)
• CD5 positive and CD23 positive
• Binet stage B, C, or progressive A
• Newly diagnosed disease OR no more than 1 prior alkylating agent regimen (e.g., chlorambucil or cyclophosphamide with or without prednisone)

PATIENT CHARACTERISTICS: Age

• 18 to 65

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• No autoimmune hemolytic anemia
• No immune thrombocytopenia

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN*
• AST and ALT no greater than 2.5 times ULN* NOTE: *Unless clearly related to CLL liver involvement

Renal

• Creatinine clearance greater than 50 mL/min

Cardiovascular

• Ejection fraction at least 50%
• No severe heart failure
• No unstable angina pectoris
• No significant arrhythmia requiring chronic treatment
• No myocardial infarction within the past 3 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after study participation
• HIV negative
• No active infection
• No positive Coombs’ test
• No history of significant neurologic or psychiatric disorders, including psychotic disorders or dementia
• No seizure disorder
• No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• No prior allergic reaction or hypersensitivity to study drugs or attributed to compounds of similar chemical or biological composition to study drugs or other study agents
• No uncontrolled diabetes mellitus
• No gastric ulcers
• No active autoimmune disease
• No alcohol or drug abuse
• No other concurrent serious underlying medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior purine analogs (e.g., cladribine or fludarabine)

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 30 days since prior clinical trial participation
• No other concurrent experimental drugs

Switzerland
      Rheinfelden,  4310,  Switzerland; Recruiting
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland; Recruiting
      Hopital des Cadolles, Neuchatel, Neuchatel,  2000,  Switzerland; Recruiting
      Inselspital, Bern, Bern,  CH-3010,  Switzerland; Recruiting
      Kantonspital Aarau, AARAU,  5001,  Switzerland; Recruiting
      Kantonsspital - St. Gallen, St. Gallen,  CH-9007,  Switzerland; Recruiting
      Kantonsspital, Luzerne, Luzerne,  CH-6000,  Switzerland; Recruiting
      Oncology Institute of Southern Switzerland, Bellinzona,  CH-6500,  Switzerland; Recruiting
      Onkozentrum, Zurich,  8038,  Switzerland; Recruiting
      Spitaler Chur AG, Chur,  CH-7000,  Switzerland; Recruiting
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland; Recruiting

Study chairs or principal investigators

Reinhard Zenhaeusern, MD,  Study Chair,  Inselspital, Bern   

Study ID Numbers:  CDR0000335110; SWS-SAKK-34/02; EU-20321; NCT00072007
Record last reviewed:  October 2003
Last Updated:  April 4, 2005
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072007
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08