DCLLSG

CLL14 Trial

Title A prospective, open-label, multicenter randomized phase III trial to compare the efficacy and safety of a combined regimen of obinutuzumab and GDC-0199 (ABT-199) versus obinutuzumab and chlorambucil in previously untreated patients with CLL and coexisting medical conditions
Protocol IDs EudraCT: 2014-001810-24
NCT02242942
Status in follow up
Contact Medical Management: Dr. Kirsten Fischer,

Dr. Kirsten Fischer
+49 221 478-88220 (Office)
kirsten.fischer@uk-koeln.de

Dr. Othman Al-Sawaf

Dr. Othman Al-Sawaf
+49 221 478-88220 (Office)
othman.al-sawaf@uk-koeln.de

Project Management: Marina Stockem

Marina Stockem
+49 221 478-85918
marina.stockem@uk-koeln.de

Contact for scientific queries Dr. Kirsten Fischer

Dr. Kirsten Fischer
+49 221 478-88220 (Office)
kirsten.fischer@uk-koeln.de

Design Prospective, open-label, randomized, multicenter phase III study
Primary Endpoint Progression-free survival (PFS) according to the IWCLL guidelines
Secondary Endpoints - PFS based on Institutional Review Committee (IRC)-assessments
- Objective response rate (ORR)
- Minimal residual disease (MRD) response rate
- Overall survival (OS)
- duration of objective response
- best response achieved (CR, CRi, PR, SD or PD)
- Event-free survival (EFS)
- Time to next anti-leukemic treatment
- AEs, SAEs
Study Population Previously untreated B-CLL according to the IWCLL guidelines, requiring treatment
Relvant comorbidities:
Total CIRS-score > 6 (< 4 for one organ category with the exception of eyes, ears, nose, throat organ system) or creatinine clearance: 30 - 70 mL/min
Age  ≥ 18 years
Treatment Arm A (Obinutuzumab + GDC-0199)
Obinutuzumab i.v.
Cycle 1: (100 mg, d1 + 900 mg, d2) oder 1000 mg, d1;
1000 mg, d8 + d15
Cycle 2 - 6: 1000 mg, d1
6 Cycles, q 28d
GDC-0199 p.o.
Cycle 1: 20 mg daily, d22–28
Cycle 2: 50 mg daily, d1–7; 100 mg daily, d8–14; 200 mg daily, d15–21; 400 mg daily, d22–28
Cycle 3 - 12: 400 mg daily, d1–28
12 Cycles, q 28d
Arm B (Obinutuzumab + Chlorambucil)
Obinutuzumab i.v.
Cycle 1: (100 mg, d1 + 900 mg, d2) oder 1000 mg, d1;
1000 mg, d8 + d15
Cycle 2 - 6: 1000 mg, d1
6 Cycles, q 28d
Chlorambucil p.o.
Cycle 1 - 12: 0,5 mg/kg, d1 + d15
12 Cycles, q 28d
Patients recruited Safety run-in phase: 13 patients
Randomized study: 432 patients
Protocol Version Protocol (Version 1 | 23 July 2014)
Amendment 1 (Version 2 | 21 Oct. 2014)
Sponsor F. Hoffmann-La Roche Ltd in collaboration with the German CLL Study Group (GCLLSG)
Co-Sponsor (US only) AbbVie, Inc.
Principal Investigator Prof. Dr. Michael Hallek, Dept. Internal Medicine I, University Hospital of Cologne
Documents
(password protected)
mystudies.roche.com
Access only with personal username and password, which have been sent to the study centers.
Publications Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions
N Engl J Med. 2019 Jun 6;380(23):2225-2236

Fischer K, Al-Sawaf O, Fink AM, Dixon M, Bahlo J, Warburton S, Kipps TJ, Weinkove R, Robinson S, Seiler T, Opat S, Owen C, López J, Humphrey K, Humerickhouse R, Tausch E, Frenzel L, Eichhorst B, Wendtner CM, Stilgenbauer S, Langerak AW, van Dongen JJ, Boettcher S, Ritgen M, Goede V, Mobasher M, Hallek M
Venetoclax and obinutuzumab in chronic lymphocytic leukemia
Blood. 2017 May 11;129(19):2702-2705

Kirsten Fischer, Anna-Maria Fink, Helen Bishop, Mark Dixon, Jasmin Bahlo, Michael Y. Choi, Robert Weinkove, K. Sue Robinson, Martin Dreyling, Till Seiler, Stephen Opat, Carolyn Owen, Javier Lopez Sr., Nadine Kutsch, Eugen Tausch, Matthias Ritgen, Rod A. Humerickhouse, Kathryn Humphrey, Michael K. Wenger, Valentin Goede, Barbara Eichhorst, Clemens-Martin Wendtner, Stephan Stilgenbauer, Thomas J. Kipps and Michael Hallek
Results of the Safety Run-in Phase of CLL14 (BO25323): A Prospective, Open-Label, Multicenter Randomized Phase III Trial to Compare the Efficacy and Safety of Obinutuzumab and Venetoclax (GDC-0199/ABT-199) with Obinutuzumab and Chlorambucil in Patients with Previously Untreated CLL and Coexisting Medical Conditions (ASH Abstract)
Blood 2015 Dec 03;126(23):496