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| 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 |
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| Protocol IDs | EudraCT: 2014-001810-24 NCT02242942 |
| Status | in follow up |
| Contact | Medical Management: Dr. Othman Al-Sawaf Dr. Othman Al-Sawaf Marie Kronmüller |
| Contact for scientific queries | Dr. Kirsten Fischer Dr. Kirsten Fischer |
| 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 |
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| 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 | Al-Sawaf O, Gentile B, Devine J, Zhang C, Sail K, Tandon M, Fink AM, Kutsch N, Wendtner CM, Eichhorst B, Hallek M, Fischer K Health-related quality of life with fixed-duration venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: Results from the randomized, phase 3 CLL14 trial Am J Hematol. 2021 May 29 doi: 10.1002/ajh.26260. Online ahead of print. Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial Lancet Oncol. 2020 Sep;21(9):1188-1200 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 |