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Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

This study has been completed.
Celgene Corporation
Roche Pharma AG
Information provided by (Responsible Party):
Arbeitsgemeinschaft medikamentoese Tumortherapie Identifier:
First received: August 20, 2008
Last updated: August 29, 2013
Last verified: August 2013

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 Intervention Phase
Leukemia, Lymphocytic, Chronic, B-Cell
Drug: Lenalidomide
Drug: Fludarabine
Biological: Rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:

Further study details as provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

Primary Outcome Measures:
  • Lenalidomide Maximum Tolerated Dose [ Time Frame: Dose escalation stage ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety profile of Lenalidomide/Fludarabine/Rituximab treatment [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
  • Safety Profile of Lenalidomide/Rituximab [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
  • Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment [ Time Frame: Dose escalation stage ] [ Designated as safety issue: No ]
  • Response rate for Lenalidomide/Rituximab combination therapy [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
  • Response rate by 4-colour flow cytometric MRD analysis [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
  • Changes in Quality of Life scores [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
  • Risk factors and clonal evolution [ Time Frame: Study Duration ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: October 2008
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00738829

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

No publications provided

Responsible Party: Arbeitsgemeinschaft medikamentoese Tumortherapie Identifier: NCT00738829     History of Changes
Other Study ID Numbers: CLL-5, EudraCT Nr. 2008-001430-27, ML21718
Study First Received: August 20, 2008
Last Updated: August 29, 2013
Health Authority: Austria: Agency for Health and Food Safety
Austria: Ethikkommission

Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:
immune therapy
dose escalation
maximum tolerated dose
maintenance therapy

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Fludarabine phosphate
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents processed this record on November 20, 2014