Title | A phase 3 multicentre, randomized, prospective, open-label trial of ibrutinib monotherapy versus fixed-duration venetoclax plus obinutuzumab versus fixed-duration ibrutinib plus venetoclax in patients with previously untreated chronic lymphocytic leukaemia (CLL) |
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Protocol IDs | EudraCT: 2019-003854-99 NCT04608318 |
Participating Countries | Austria, Belgium, Denmark, Finland, Germany, Ireland, Israel, Italy, Netherlands, Norway, Spain, Sweden, Switzerland |
Status | Recruiting |
Contact | Medical Management: Dr. Othman Al-Sawaf Dr. Othman Al-Sawaf Aline Zey Jan-Erik Mittler Tanja Annolleck |
Contact for scientific queries | Dr. Othman Al-Sawaf Dr. Othman Al-Sawaf |
Design | Prospective, multicentre, open-label, randomized phase-III trial |
Primary Endpoint | Progression-free survival (PFS) |
Secondary Endpoints | - Rates of undetectable MRD in peripheral blood (PB) and bone marrow (BM) at final restaging (RE) and additional BM assessment approx. 12 months after RE - MRD levels in PB at different time points - Duration of undetectable MRD (uMRD) - Overall response rate (ORR) - Complete response rate (CRR) - Overall survival (OS) - Event-free survival (EFS) (I vs VG and I vs VI) - Time to next treatment (TTNT) - PFS2 (i.e. PFS after second-line treatment) Safety parameters: Type, frequency, and severity and their relationship to study treatment of AEs, AESs, AEPIs and/or Tumour lysis syndrome (TLS) Exploratory analyses: - Evaluation of relationship between various baseline markers and clinical outcome parameters (e.g. PFS, OS, ORR relative to del17p/TP53, IGHV, fitness, etc) - MRD by methods other than flow cytometry - Correlation between MRD in BM and PB - Correlation between MRD in BM and PFS/ EFS/ OS Correlation between MRD in PB and PFS/ EFS/ OS - Health-related quality of life by EORTC QLQC30 and QLQ-CLL17 questionnaires - Medical Resource Utilization |
Study Population | Previously untreated B-CLL according to the IWCLL guidelines, requiring treatment Creatinine clearance (GFR) >30ml/min ECOG performance status 0-2 Age ≥ 18 years |
Treatment | Arm I (Ibrutinib) Ibrutinib p.o. Cycles 1 - X: 420 mg daily, d1–28 |
Arm VG (Obinutuzumab + Venetoclax) 12 Cycles, q 28d Obinutuzumab i.v. Cycle 1: (100 mg, d1 + 900 mg, d2) or 1000 mg, d1; 1000 mg, d8 + d15 Cycle 2 - 6: 1000 mg, d1 Venetoclax p.o. (ramp-up: dose escalation until final dose is reached) Cycle 1: 20 mg (2 tabl. at 10 mg), d22-28 Cycle 2: 50 mg (1 tabl. at 50 mg), d1-7; 100 mg (1 tabl. at 100 mg), d8-14; 200 mg (2 tabl. at 100 mg), d15-21; 400 mg (4 tabl. at 100 mg), d22-28 Cycles 3-12: 400 mg (4 tabl. at 100 mg), d1-28 |
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Arm VI (Venetoclax + Ibrutinib) 15 Cycles, q 28d Ibrutinib p.o. Cycles 1 - 15: 420 mg daily, d1–28 Venetoclax p.o. (ramp-up: dose escalation until final dose is reached) Cycle 4: 20 mg (2 tabl. at 10 mg), 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 100 mg), d22-28 Cycles 5-15: 400 mg (4 tabl. at 100 mg), d1-28 |
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Targeted Accrual | Approximately 897 eligible patients |
Time schedule | Start of recruitment: Q4/2020 Expected end of recruitment: Q4/2023 End of trial: Q3/2027 |
Protocol Version | Protocol (Version 1.2 | 23 Sep 2020) |
Sponsor | University of Cologne |
Global Principal Investigator | Dr. med. Othman Al-Sawaf, Department I of Internal Medicine, Cologne University Hospital |
Documents (publicly available) |
Synopsis (Version 1.2 | 23 Sep 2020) |
Documents (password protected) |
Protocol and other documents see Download Center |