Clinical trial NCT00072007: Cladribine and Rituximab as Remission Induction Therapy Followed By Rituximab and Stem Cell Mobilization in Treating Patients With CLL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: 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
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2003-11-06
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete-remission rate after induction
timeFrame: 30 days
Secondary outcomes:
measure: Very good partial remission and nodular partial remission after induction
timeFrame: 30 days
measure: Toxicity (hematotoxicity and infection rate) at 30 days following study treatment
timeFrame: 30 days
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Chur
country: Switzerland
facility: Spitaeler Chur AG
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Luzerne
country: Switzerland
facility: Kantonsspital, Luzerne
city: Neuchatel
country: Switzerland
facility: Hopital des Cadolles, Neuchatel
city: Rheinfelden
country: Switzerland
facility: Praxis Dr. Beretta
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Zurich
country: Switzerland
facility: Onkozentrum
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Reinhard Zenhaeusern, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.