Cladribine and Rituximab as Remission Induction Therapy Followed By Rituximab and Stem Cell Mobilization in Treating Patients With CLL

NCT ID: NCT00072007

Last Updated: 2012-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30
• Study Completion Date: 2010-10-31

Brief Summary

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: This phase II trial is studying how well giving cladribine and rituximab as remission induction therapy together with rituximab and stem cell mobilization in treating patients with chronic lymphocytic leukemia.

Detailed Description

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.

• Remission induction: 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.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

filgrastim

filgrastim

Intervention Type: BIOLOGICAL

rituximab

rituximab

Intervention Type: BIOLOGICAL

CHOP regimen

CHOP regimen

Intervention Type: DRUG

cladribine

cladribine

Intervention Type: DRUG

cyclophosphamide

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

doxorubicin hydrochloride

Intervention Type: DRUG

prednisone

prednisone

Intervention Type: DRUG

vincristine sulfate

vincristine sulfate

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Reinhard Zenhaeusern, MD

Role: STUDY_CHAIR

Insel Gruppe AG, University Hospital Bern

Locations

Kantonspital Aarau

Aarau, , Switzerland

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitaeler Chur AG

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital, Luzerne

Luzerne, , Switzerland

Hopital des Cadolles, Neuchatel

Neuchâtel, , Switzerland

Praxis Dr. Beretta

Rheinfelden, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Onkozentrum

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

References

Leupin N, Schuller JC, Solenthaler M, Heim D, Rovo A, Beretta K, Gregor M, Bargetzi MJ, Brauchli P, Himmelmann A, Hanselmann S, Zenhausern R. Efficacy of rituximab and cladribine in patients with chronic lymphocytic leukemia and feasibility of stem cell mobilization: a prospective multicenter phase II trial (protocol SAKK 34/02). Leuk Lymphoma. 2010 Apr;51(4):613-9. doi: 10.3109/10428191003624231.

Reference Type: RESULT

PMID: 20218808 (View on PubMed)

Leupin N, Schuller JC, Solenthaler M, et al.: The combination of 2-CDA and rituximab in patients with chronic lymphocytic leukemia (CLL): a prospective multicenter phase II trial (SAKK 34/02). [Abstract] Blood 110 (11): A-2057, 2007.

Reference Type: RESULT

Other Identifiers

EU-20321

Identifier Type: -

Identifier Source: secondary_id

SAKK 34/02

Identifier Type: -

Identifier Source: org_study_id