Cladribine and Rituximab as Remission Induction Therapy Followed By Rituximab and Stem Cell Mobilization in Treating Patients With Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00072007

Purpose

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.

Condition	Intervention	Phase
Leukemia	Biological: filgrastim Biological: rituximab Drug: CHOP regimen Drug: cladribine Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Filgrastim Lenograstim Granulocyte colony-stimulating factor Rituximab Vincristine sulfate Cladribine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete-remission rate after induction [ Designated as safety issue: No ]

Secondary Outcome Measures:

Very good partial remission and nodular partial remission after induction [ Designated as safety issue: No ]
Toxicity (hematotoxicity and infection rate) at 30 days following study treatment [ Designated as safety issue: Yes ]

Estimated Enrollment:	41
Study Start Date:	June 2002

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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00072007

Locations

Switzerland
Kantonspital Aarau
Aarau, Switzerland, 5001
Oncology Institute of Southern Switzerland
Bellinzona, Switzerland, CH-6500
Inselspital Bern
Bern, Switzerland, CH-3010
Spitaeler Chur AG
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital, Luzerne
Luzerne, Switzerland, CH-6000
Hopital des Cadolles, Neuchatel
Neuchatel, Switzerland, 2000

Rheinfelden, Switzerland, 4310
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Onkozentrum
Zurich, Switzerland, 8038

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:

Reinhard Zenhaeusern, MD

University Hospital Inselspital, Berne

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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 mobilization: a prospective multicenter phase II trial (protocol SAKK 34/02). Leuk Lymphoma. 2010 Mar 10; [Epub ahead of print]

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.

ClinicalTrials.gov Identifier:	NCT00072007 History of Changes
Other Study ID Numbers:	CDR0000335110, SWS-SAKK-34/02, EU-20321
Study First Received:	November 4, 2003
Last Updated:	June 21, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cladribine
Rituximab
Doxorubicin
Prednisone

Vincristine
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids

ClinicalTrials.gov processed this record on February 09, 2012