CLLM1 Trial

Title A phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of lenalidomide (Revlimid®) as maintenance therapy for high-risk patients with chronic lymphocytic leukemia following first-line therapy
Protocol IDs EUDRACT-2011-004698-98
Recruitment Status prematurely terminated due to slow recruitment rate;
trial in follow up
Contact Medical Management: Dr. Anna Fink

Dr. Anna Fink
+49 221 478-88198

Project Management: Aline Zey

Aline Zey
+49 221 478-96577

Data Management: Jan-Erik Mittler

Jan-Erik Mittler
+49 221 478-88199

Safety Management: Sabine Frohs

Sabine Frohs
+49 221 478-89621

Contact for scientific queries Dr. Anna Fink

Dr. Anna Fink
+49 221 478-88198

Design Prospective, multicenter, randomized, double-blind, placebo-controlled,
parallel-group phase III study
Primary Endpoint(s) Progression-Free Survival (PFS) based on independent review
Secondary Endpoints - Progression free survival (PFS) – assessed by the investigator
- Overall survival (OS)
- Safety (AEs, premature terminations of the trial)
- Assessment of Minimal Residual Disease (MRD)
- Quality of life (EORTC QLQ C30 and EQ-5D)
- Time until next treatment
- Event free survival (EFS)
- Treatment free interval after secondary therapy
Study Population B-CLL according to the IWCLL guidelines
- Must have been treated with one of the first line induction therapies:
fludarabine/cyclophosphamide/rituximab, or bendamustine/rituximab or
fludarabine/rituximab or fludarabine/cyclophosphamide,(in case of
hypersensitivity reactions to Rituximab).
- Must have achieved a response of at least PR (according to the IWCLL guidelines) following completion (minimum 4 cycles) of first-line induction therapy prior to randomization (documentation of response status must be available).
and have either:
a. MRD levels in the peripheral blood at final restaging of ≥ 10-2 or
b. MRD levels in the peripheral blood ≥10-4 - <10-2 combined with at
least one of the following factors:
      • an unmutated IGHV-status
      • 17p-deletion or
      • TP53 mutation
Must have completed last cycle of at least 4 cycles of first-line induction no less than 8 weeks (56 days) and no greater than 20 weeks (140 days) prior to randomization
ECOG ≤ 2
CIRS-Score ≤ 6 and no single score of ≥ 4 for an organ system
Age  ≥ 18 years

Exclusion criteria: Autologous or allogeneic bone marrow transplant as first line therapy, Prior therapy with lenalidomide, Richter’s Syndrome
Treatment Daily administration of placebo or lenalidomide in a 28-day cycle until disease progression, unacceptable toxicity or voluntary treatment withdrawal, whichever occurs first.
Dose escalation from 5 mg up to a maximal daily dose of 25 mg if well tolerated and MRD levels are ≥ 10-4.
Enrollment 89 patients
Time schedule Recruitment period: 20 July 2012 - 24 January 2016
Activation of Amendment 1: 12 February 2014
Activation of Amendment 2: 11 August 2014
Activation of Amendment 3: 26 January 2016
Activation of Amendment 4: 04 July 2016
Activation of Amendment 5: 20 December 2016
Estimated end of study: 03/2021
Protocol Version Protocol (V. 2.1 / 04 June 2012)
Amendment 1 (V. 3.0 / 05 July 2013)
Amendment 3 (V. 4.0 / 20 October 2015)
Amendment 5 (V. 5.0 / 11 October 2016)
Sponsor University of Cologne
Principal Investigator Prof. Dr. Barbara Eichhorst, Internal Medicine I, University Hospital of Cologne
(publicly available)
Synopsis (V. 5.0 / 11 October 2016)
(password protected)
Protocol and other documents see Download Center
Publications Fink AM, Bahlo J, Robrecht S, Al-Sawaf O, Aldaoud A, Hebart H, Jentsch-Ullrich K, Dörfel S, Fischer K, Wendtner CM, Nösslinger T, Ghia P, Bosch F, Kater AP, Döhner H, Kneba M, Kreuzer KA, Tausch E, Stilgenbauer S, Ritgen M, Böttcher S, Eichhorst B, Hallek M
Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study
Lancet Haematol. 2017 Sep 12 pii: S2352-3026(17)30171-0. doi: 10.1016/S2352-3026(17)30171-0. [Epub ahead of print]