Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL
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.
Leukemia, Lymphocytic, Chronic, B-Cell
|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.|
- Lenalidomide Maximum Tolerated Dose [ Time Frame: Dose escalation stage ] [ Designated as safety issue: Yes ]
- 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 ]
|Study Start Date:||October 2008|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment Arm
Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy
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: RevlimidDrug: 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 phosphateBiological: 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
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.
|Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie|
|Innsbruck, Tirol, Austria, A-6020|
|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|
|Principal Investigator:||Richard Greil, Prof. Dr.||Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg|