Title | A prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of zanubrutinib (BGB-3111), a BTK inhibitor, plus tislelizumab (BGB-A317), a PD1 inhibitor, for treatment of patients with Richter Transformation |
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Protocol IDs | EudraCT: 2018-002492-17 NCT04271956 |
Participating Countries | Germany, Austria, Denmark |
Status | Recruiting |
Contact | Medical Management: Dr. Othman Al-Sawaf Dr. Othman Al-Sawaf Laura Miesen Laura Miesen Dr. Emily Holmes Henrik Gerwin Henrik Gerwin Jan-Erik Mittler Sabine Frohs |
Contact for scientific queries | Prof. Dr. Barbara Eichhorst Prof. Dr. Barbara Eichhorst Dr. Othman Al-Sawaf |
Design | Prospective, multicenter, single-arm, open-label phase-II trial |
Objective | To evaluate the efficacy and the safety of the combinational therapy |
Primary Endpoint | Overall response rate (ORR) after induction therapy (6 cycles) according to the refined Lugano Classification (Cheson et al, 2016) - Complete response (CR) - Partial response (PR) |
Secondary Endpoints | - ORR after induction therapy (6 cycles) according to
iwCLL Kriterien (Hallek et al, 2018) - ORR after consolidation therapy (i.e. 12 cycles) - Duration of response - Progression-free survival (PFS) - Overall survival (OS) - Time to next treatment (TTNT) - Proportion of patients receiving SCT for consolidation - Exploratory endpoints: Evaluation of relationship between various baseline markers, including PD-1/PD-L1 expression and mutational load, and clinical outcome parameters - Safety parameters: type, frequency, severity of adverse events (AEs), and their relationship to study treatment |
Target Population | - Confirmed B-CLL according to iwCLL criteria - Confirmed histopathological diagnosis of Richter Transformation (RT) - Previously untreated RT or up to 1 RT therapy with response - ECOG performance status 0 – 2 (ECOG 3 only permitted if related to CLL or RT) - Age ≥ 18 years |
Treatment | Induction 6 Cycles, q 21d Tislelizumab i.v. Cycle 1 - 6: 200 mg, d1 + Zanubrutinib p.o. Cycle 1 - 6: 160 mg, twice daily |
Consolidation 6 Cycles, q 21d Tislelizumab i.v. Cycle 7 - 12: 200 mg, d1 + Zanubrutinib p.o. Cycle 7 - 12: 160 mg, twice daily |
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Maintenance Patients with response to therapy continue to take both agents until - disease progression, - non-tolerance or when - receiving allogenic SCT for consolidation |
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Targeted Accrual | 48 patients |
Time schedule | Recruitment period: Q1/2020 - Q1/2022 End of study: Q2/2023 |
Protocol Version | 19 Jun 2019 Protocol (Version 1.2) 16 Oct 2020 Amendment 1 (Version 2.0) |
Sponsor | University of Cologne |
Principal Investigator | Prof. Dr. Barbara Eichhorst, Department I of Internal Medicine, University Hospital of Cologne |
Coordinating Physician | Dr. Othman Al-Sawaf, Department I of Internal Medicine, University Hospital of Cologne |
Documents (publicly available) |
Synopsis (Version 2.0 | 16 Oct 2020) |
Documents (password protected) |
Protocol and other documents see Download Center |