Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

August 29, 2013 updated by: Arbeitsgemeinschaft medikamentoese Tumortherapie

Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Concomitant Evaluation of Safety and Efficacy.

The aim of this study is to determine the maximal tolerated dose level of lenalidomide combined with fludarabine/rituximab in the therapy of patients with previously untreated CD20-positive chronic lymphocytic leukemia. Following a dose escalation phase lenalidomide will be given at the pre-determined maximum tolerated dose in combination with rituximab to further determine the efficacy and tolerability of this regimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a non-randomized, multicenter, open-label, single-arm Phase I/II study in patients with previously untreated CD20-positive CLL. Phase I of the study will evaluate the maximal tolerated lenalidomide dose level in combination with fludarabine/rituximab chemoimmunotherapy in 10 patients. Phase II will determine efficacy using the combination in the previously defined maximal tolerated dose. Both phases will be followed by a maintenance phase evaluating the tolerability and possibility to further improve response quality.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2
  • Phase 1

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

  • Austria
      • Feldkirch, Austria, A-6806
        • Landeskrankenhaus Feldkirch
      • Linz, Austria, A-4010
        • Krankenhaus der Elisabethinen Linz GmbH
      • Linz, Austria, A-4010
        • Krankenhaus d. Barmherzigen Schwestern Linz
      • Linz, Austria, A-4020
        • Krankenhaus der Stadt Linz
      • Salzburg, Austria, A-5020
        • Universitaetsklinik f. Innere Medizin III
      • Wels, Austria, A-4600
        • Klinikum Wels-Grieskirchen GmbH
    • Tirol
      • Innsbruck, Tirol, Austria, A-6020
        • Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • B-CLL (CD23+, CD5+, CD19+, CD20+)
  • Treatment indication according to NCI criteria
  • Age >= 18 yrs
  • No previous treatment of CLL by chemo-, radio- or immunotherapy
  • Life expectancy > 6 months
  • Written informed consent
  • Women of non-childbearing potential or women of childbearing potential and men using effective contraception

Exclusion Criteria:

  • Active bacterial, viral or fungal infection
  • Positivity for HIV, Hepatitis B or C
  • Reduce organ functions and bone marrow dysfunction not due to CLL
  • Creatinine clearance below 30 ml/min
  • Patients with medical conditions requiring long-term use of systemic corticosteroids during study treatment
  • Patients with a history of severe cardiac disease
  • Other known co-morbidity with the potential to dominate survival
  • Transformation to aggressive B-cell malignancy
  • Known hypersensitivity to humanised monoclonal antibodies or any of the study drugs
  • Pregnant or breast-feeding women
  • Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment Arm
Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy
Drug: Lenalidomide

Dose escalation stage: starting dose 2.5mg/d, dose escalation via 5/10/15/20/25 mg/d every 28 days if no dose-limiting toxicity.

During maintenance stage dosing on days 1-28 for max. 6 months at maximum tolerated dose reached during dose escalation stage.

Other Names:
  • Revlimid
Drug: Fludarabine
25 mg/m2 i.v. d1-3 or 40 mg/m2 po d1-3 every 28 days for 6 cycles during dose escalation stage.
Other Names:
  • Fludarabine phosphate
Biological: Rituximab

Dose escalation stage: 375 mg/m2 i.v. d4 Cycle 1, 500 mg/m2 i.v. d1 Cycles 2-6.

Maintenance stage: 375 mg/m2 i.v. at 2/4/6 months after end of escalation stage.

Other Names:
  • MabThera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Lenalidomide Maximum Tolerated Dose
Time Frame: Dose escalation stage
Dose escalation stage

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety profile of Lenalidomide/Fludarabine/Rituximab treatment
Time Frame: Study Duration
Study Duration
Safety Profile of Lenalidomide/Rituximab
Time Frame: Study duration
Study duration
Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment
Time Frame: Dose escalation stage
Dose escalation stage
Response rate for Lenalidomide/Rituximab combination therapy
Time Frame: Study Duration
Study Duration
Response rate by 4-colour flow cytometric MRD analysis
Time Frame: Study Duration
Study Duration
Changes in Quality of Life scores
Time Frame: Study Duration
Study Duration
Risk factors and clonal evolution
Time Frame: Study Duration
Study Duration

Collaborators and Investigators

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

Sponsor

Arbeitsgemeinschaft medikamentoese Tumortherapie

Collaborators

Roche Pharma AG
Celgene Corporation

Investigators

  • Principal Investigator: Richard Greil, Prof. Dr., Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg

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

October 1, 2008

Primary Completion (ACTUAL)

January 1, 2012

Study Completion (ACTUAL)

January 1, 2012

Study Registration Dates

First Submitted

August 20, 2008

First Submitted That Met QC Criteria

August 20, 2008

First Posted (ESTIMATE)

August 21, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

August 30, 2013

Last Update Submitted That Met QC Criteria

August 29, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL-5
  • EudraCT Nr. 2008-001430-27
  • ML21718

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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