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

May 14, 2012 updated by: Swiss Group for Clinical Cancer Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Aarau, Switzerland, 5001
        • Kantonspital Aarau
      • Bellinzona, Switzerland, CH-6500
        • Oncology Institute of Southern Switzerland
      • Bern, Switzerland, CH-3010
        • Inselspital Bern
      • Chur, Switzerland, CH-7000
        • Spitaeler Chur AG
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Luzerne, Switzerland, CH-6000
        • Kantonsspital, Luzerne
      • Neuchatel, Switzerland, 2000
        • Hopital des Cadolles, Neuchatel
      • Rheinfelden, Switzerland, 4310
        • Praxis Dr. Beretta
      • St. Gallen, Switzerland, CH-9007
        • Kantonsspital - St. Gallen
      • Zurich, Switzerland, 8038
        • Onkozentrum
      • Zurich, Switzerland, CH-8091
        • Universitaetsspital Zuerich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Group for Clinical Cancer Research

Investigators

  • Study Chair: Reinhard Zenhaeusern, MD, University Hospital Inselspital, Berne

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (Actual)

March 1, 2003

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

November 4, 2003

First Submitted That Met QC Criteria

November 5, 2003

First Posted (Estimate)

November 6, 2003

Study Record Updates

Last Update Posted (Estimate)

May 15, 2012

Last Update Submitted That Met QC Criteria

May 14, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 34/02
  • EU-20321

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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