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Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00738829
Recruitment Status : Completed
First Posted : August 21, 2008
Last Update Posted : August 30, 2013
Celgene Corporation
Roche Pharma AG
Information provided by (Responsible Party):
Arbeitsgemeinschaft medikamentoese Tumortherapie

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Leukemia, Lymphocytic, Chronic, B-Cell Drug: Lenalidomide Drug: Fludarabine Biological: Rituximab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : October 2008
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

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 Name: 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 Name: 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 Name: MabThera

Primary Outcome Measures :
  1. Lenalidomide Maximum Tolerated Dose [ Time Frame: Dose escalation stage ]

Secondary Outcome Measures :
  1. Safety profile of Lenalidomide/Fludarabine/Rituximab treatment [ Time Frame: Study Duration ]
  2. Safety Profile of Lenalidomide/Rituximab [ Time Frame: Study duration ]
  3. Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment [ Time Frame: Dose escalation stage ]
  4. Response rate for Lenalidomide/Rituximab combination therapy [ Time Frame: Study Duration ]
  5. Response rate by 4-colour flow cytometric MRD analysis [ Time Frame: Study Duration ]
  6. Changes in Quality of Life scores [ Time Frame: Study Duration ]
  7. Risk factors and clonal evolution [ Time Frame: Study Duration ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00738829

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Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie
Innsbruck, Tirol, Austria, A-6020
Landeskrankenhaus Feldkirch
Feldkirch, Austria, A-6806
Krankenhaus d. Barmherzigen Schwestern Linz
Linz, Austria, A-4010
Krankenhaus der Elisabethinen Linz GmbH
Linz, Austria, A-4010
Krankenhaus der Stadt Linz
Linz, Austria, A-4020
Universitaetsklinik f. Innere Medizin III
Salzburg, Austria, A-5020
Klinikum Wels-Grieskirchen GmbH
Wels, Austria, A-4600
Sponsors and Collaborators
Arbeitsgemeinschaft medikamentoese Tumortherapie
Celgene Corporation
Roche Pharma AG
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Principal Investigator: Richard Greil, Prof. Dr. Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Arbeitsgemeinschaft medikamentoese Tumortherapie Identifier: NCT00738829    
Other Study ID Numbers: CLL-5
EudraCT Nr. 2008-001430-27
First Posted: August 21, 2008    Key Record Dates
Last Update Posted: August 30, 2013
Last Verified: August 2013
Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:
immune therapy
dose escalation
maximum tolerated dose
maintenance therapy
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine phosphate
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antiviral Agents
Anti-Infective Agents