DCLLSG

CLL17 Trial

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

Project Management: Aline Zey

Aline Zey
+49 221 478-96577
aline.zey@uk-koeln.de

Data Management: Jan-Erik Mittler

Jan-Erik Mittler
+49 221 478-88199
jan-erik.mittler@uk-koeln.de

Safety Management: Tanja Annolleck

Tanja Annolleck
+49 221 478-96579
tanja.annolleck@uk-koeln.de

Contact for scientific queries Dr. Othman Al-Sawaf

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

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
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
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
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Protocol and other documents see Download Center