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| Title | A prospective, open-label, multicentre phase-II trial of ibrutinib plus venetoclax plus obinutuzumab in physically fit (CIRS ≤ 6 & normal creatinine clearance) and unfit (CIRS > 6 & creatinine clearance ≥ 50 ml/min) patients with previously untreated chronic lymphocytic leukemia (CLL) with TP53 deletion (17p-) and/or mutation |
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| Protocol IDs | EudraCT: 2015-004606-41 NCT02758665 |
| Status | in follow up |
| General Inquiries | cll2-give@uk-koeln.de |
| Contact | Medical Management: Dr. Moritz Fürstenau Dr. Moritz Fürstenau Angelina Glatt Irene Preißler-Stodden Sabine Frohs |
| Contact for scientific queries | Prof. Dr. Stephan Stilgenbauer Prof. Dr. Stephan Stilgenbauer |
| Design | Prospective, open-label, multicentre phase-II trial |
| Objective | Evaluation of the efficacy of the GIVe regimen in patients with TP53 deletion (17p-) and/or mutation and previously untreated CLL requiring treatment |
| Primary Endpoint | Complete response (CR) rate at cycle 15 (d1; at final restaging) |
| Secondary Endpoints | - Proportion of patients free of disease progression (PD-free rate)
after 12 cycles of therapy - Overall response rate (ORR) - ORR after end of maintenance treatment - MRD levels (measured in peripheral blood after cycle 9, after cycle 12, at the beginning of cycle 15 (d1), at the beginning of cycle 36 (d1), as well as in bone marrow at the beginning of cycle 15) - Progression-free survival (PFS) - Event-free survival (EFS) - Overall survival (OS) - Duration of response in patients with (clinical) CR/CRi, PR - Treatment-free survival (TFS) and time to next CLL treatment (TTNT) - Evaluation of subsequent treatment for CLL (including proportion receiving allogeneic SCT as consolidation or in relapse) including response to treatment - Safety parameters: Type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment - Incidence of Richter’s transformation - Exploratory: Evaluation of relationship between baseline markers and clinical outcome parameters |
| Target Population | - CLL according to iwCLL criteria, requiring treatment - Previously untreated CLL - ECOG performance status ≤ 2 Creatinine clearance ≥ 50 ml/min - Age ≥ 18 years |
| Treatment | Obinutuzumab (GA010) i.v.
Cycle 1: d1 - 100 mg, d1 (or d2) - 900 mg, d8 + d15 - 1000 mg Cycle 2 - 6: 1000 mg, d1 6 cycles, q 28d Ibrutinib p.o. 420 mg daily beginning with d1 of cycle 1 Venetoclax (ABT-199/GDC-0199) p.o. Cycle 1: d22-28 - 20 mg (2 tabl. at 10 mg) Cycle 2: d1-7 - 50 mg (1 tabl. at 50 mg), d8-14 - 100 mg (1 tabl. at 100 mg), d15-21 - 200 mg (2 tabl. at à 100 mg), d22-28 - 400 mg (4 tabl. at 100 mg) Cycle 3-12: d1-28 - 400 mg (4 tabl. at 100 mg) 12 cycles, q 28d |
| Patients recruited | 41 patients |
| Time schedule | Recruitment period: 29 Sept 2016 - 19 Oct 2018
End of study: Q1/2022 Final study report: Q1/2023 |
| Protocol Version | 20 July 2016 Protocol (Version 1.1) 22 Nov. 2016 Amendment 1 (Version 1.2) 28 Nov. 2017 Amendment 2 (Version 1.3) 30 Jan 2019 Amendment 3 (Version 1.4) 27 Jul 2020 Amendment 4 (Version 1.5) |
| Sponsor | Ulm University |
| Global Principal Investigator | Prof. Dr. med. Stephan Stilgenbauer, Department III of Internal Medicine, University Hospital of Ulm |
| Coordinating Physicians | Dr. med. Christof Schneider, University Hospital of Ulm Dr. med. Moritz Fürstenau, University Hospital of Cologne |
| Documents (password protected) |
Protocol and documents see Download Center |