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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00072007
• Other study ID #: SAKK 34/02
• Secondary ID: EU-20321
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2003
• Last updated: May 14, 2012
• Start date: June 2002
• Est. completion date: October 2010

Study information

• Verified date: May 2012
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: October 2010
• Est. primary completion date: March 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• filgrastim
filgrastim
• rituximab
rituximab

Drug:
• CHOP regimen
CHOP regimen
• cladribine
cladribine
• cyclophosphamide
cyclophosphamide
• doxorubicin hydrochloride
doxorubicin hydrochloride
• prednisone
prednisone
• vincristine sulfate
vincristine sulfate

Locations

Country	Name	City	State
Switzerland	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	Neuchatel
Switzerland	Praxis Dr. Beretta	Rheinfelden
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Onkozentrum	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

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.

Leupin N, Schuller JC, Solenthaler M, Heim D, Rovo A, Beretta K, Gregor M, Bargetzi MJ, Brauchli P, Himmelmann A, Hanselmann S, Zenhäusern R. Efficacy of rituximab and cladribine in patients with chronic lymphocytic leukemia and feasibility of stem cell m — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete-remission rate after induction		30 days	No
Secondary	Very good partial remission and nodular partial remission after induction		30 days	No
Secondary	Toxicity (hematotoxicity and infection rate) at 30 days following study treatment		30 days	Yes