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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Leukemia

Intervention / Treatment
-----------------
* Biological: filgrastim
* Biological: rituximab
* Drug: CHOP regimen
* Drug: cladribine
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|filgrastim|
|Biological: rituximab|rituximab|
|Drug: CHOP regimen|CHOP regimen|
|Drug: cladribine|cladribine|
|Drug: cyclophosphamide|cyclophosphamide|
|Drug: doxorubicin hydrochloride|doxorubicin hydrochloride|
|Drug: prednisone|prednisone|
|Drug: vincristine sulfate|vincristine sulfate|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete-remission rate after induction |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Very good partial remission and nodular partial remission after induction |  | 30 days | 
| Toxicity (hematotoxicity and infection rate) at 30 days following study treatment |  | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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