2-CDA and Rituximab as Remission Induction and Rituximab as In Vivo Purging Prior to Peripheral Stem Cell Mobilization in Patients With Chronic Lymphocytic Leukemia (CLL) - A Prospective Multicenter Phase II Trial
18 Years
65 Years
Both
Leukemia
Trial Information
2-CDA and Rituximab as Remission Induction and Rituximab as In Vivo Purging Prior to Peripheral Stem Cell Mobilization in Patients With Chronic Lymphocytic Leukemia (CLL) - A Prospective Multicenter Phase II Trial
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete-remission rate after induction
Outcome Time Frame:
30 days
Safety Issue:
No
Principal Investigator
Reinhard Zenhaeusern, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University Hospital Inselspital, Berne
Authority:
Switzerland: Swissmedic
Study ID:
SAKK 34/02
NCT ID:
NCT00072007
Start Date:
June 2002
Completion Date:
October 2010
Related Keywords:
- Leukemia
- 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
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
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