Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL)
The primary objective of this study is to determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy according to NCI response criteria (also established according to IWCLL guidelines) upon treatment with a combination of bendamustine and alemtuzumab.
Leukemia, Lymphocytic, Chronic, B-Cell
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL) - A Phase I/II Trial With Concomitant Evaluation of Safety and Efficacy|
- To determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy [ Time Frame: 2 -16 months ] [ Designated as safety issue: No ]
- To evaluate the efficacy of a bendamustine/ alemtuzumab combination therapy in terms of complete response rates [ Time Frame: 2 - 16 months ] [ Designated as safety issue: No ]
- To evaluate the achievable cumulative doses of bendamustine and alemtuzumab in terms of maximum tolerated doses while on treatment [ Time Frame: 2 -16 months ] [ Designated as safety issue: Yes ]
- To determine response rates in all phases by 4-colour flow cytometric MRD analysis [ Time Frame: 2 -16 months ] [ Designated as safety issue: No ]
- To identify and characterize potential risk factors via FISH cytogenetics, CD38/ Zap-70 expression and mutational status [ Time Frame: 2 - 6 months ] [ Designated as safety issue: No ]
- To define clonal evolution by use of longitudinal FISH cytogenetics [ Time Frame: 2 - 6 months ] [ Designated as safety issue: No ]
- To define T cell subsets including prognostic EM T cells and Treg cells [ Time Frame: 2 - 16 months ] [ Designated as safety issue: No ]
- To document change upon quality of life by use of a standardized QoL questionnaire [ Time Frame: 2 -16 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2009|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Dose escalation phase:
Days -3, -2, -1: 3 - 10 - 30 mg Alemtuzumab s.c.
Bendamustine 70 mg/m2 i.v. on d1 + d2 repeat every 28 days for 4 cycles
Alemtuzumab 30 mg s.c. 3x per week (days 1, 3, 5) continuously in parallel with chemotherapy cycles for a maximum of 16 weeks
This is a non-randomized, multicenter, open-label, single-arm Phase I/II study to evaluate the safety and efficacy of bendamustine combined with alemtuzumab in patients with pretreated CD20-positive CLL (according to the revised NCI/ IWCLL criteria).
Eligible patients will receive bendamustine as 4 courses of 70 mg/m2 on days 1 and 2 every 28 days and 30 mg alemtuzumab s.c. continuously on days 1, 3 and 5 of every week, for a maximum of 16 weeks. Safety assessments will be conducted weekly; efficacy assessments including imaging will be performed at months 2, 4, 6, 10 and 16. Bone marrow biopsies will be performed upon CR (according to the 2008 IWCLL response criteria) or fixed at 6 and 16 months.
Following recruitment of the first 3 and 7 patients safety evaluations will be performed by a data safety monitoring board. An interim analysis for response and safety as well as maximum tolerated dose levels will occur after the first 7 patients have completed treatment (Gehan timepoint). If the treatment is deemed clinically safe a further 13 patients will be enrolled.
|Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie|
|Innsbruck, Tirol, Austria, A-6020|
|Feldkirch, Austria, A-6806|
|A.ö. Landeskrankenhaus Leoben|
|Leoben, Austria, A-8700|
|Krankenhaus der Elisabethinen Linz|
|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|
|Study Chair:||Richard Greil, Prof.Dr.||Arbeitsgemeinschaft medikamentoese Tumortherapie|