Protocol description of the HOVON 141/VISION trial: a prospective, multicentre, randomised phase II trial of ibrutinib plus venetoclax in patients with creatinine clearance ≥30 mL/min who have relapsed or refractory chronic lymphocytic leukaemia (RR-CLL) with or without TP53 aberrations

Abstract

Introduction: Literature is scarce on the combination treatment of ibrutinib and venetoclax (IV) is scarce in relapsed or refractory chronic lymphocytic leukaemia (RR-CLL). Especially, the possibility of stopping ibrutinib in RR-CLL patients in deep remission is unclear.

Methods and analysis: In the HOVON 141/VISION trial, patients with RR-CLL are treated with 12 cycles of IV after a short induction with ibrutinib. Patients reaching undetectable minimal residual disease (uMRD) after 12 cycles of IV are randomised 1:2 to continue ibrutinib or stop treatment. The persistence of uMRD after stopping IV is studied. In addition, in patients who become positive for MRD again after stopping, IV treatment is reinitiated. The efficacy of this approach with regard to progression-free survival 12 months after randomisation is the primary endpoint of the study.

Ethics and dissemination: This protocol respects the Helsinki declaration and has been approved by the ethical committee of the Amsterdam Medical Center. Study findings will be disseminated through peer-reviewed papers. All patients who fulfil the inclusion criteria and no-exclusion criteria, and have signed the informed consent form are included in the study.

Trial registration number: ClinicalTrials.gov Registry (NCT03226301).

Keywords: clinical trials; leukaemia; lymphoma; toxicity.

Conflict of interest statement

Competing interests: M-DL: Advisory board compensation from Janssen, AbbVie and Roche; travel reimbursement from Janssen, AbbVie and Roche. AK: Received research grants from Celgene, Janssen, AbbVie, Roche/Genentech, AstraZeneca; speakers fee from AbbVie and AstraZeneca, and participated in advisory boards of AbbVie, Janssen, AstraZeneca and Roche. CUN: Research grant from AbbVie and Janssen; advisory board compensation from AbbVie, Janssen, Gilead, Roche, AstraZeneca, Acerta and Sunesis; travel reimbursement from Gilead, Roche and Novartis; consultancy compensation from CSL Behring. MM: Lecture remuneration from Janssen and advisory board compensation from AbbVie. JR: Received consultancy fees from AbbVie and Janssen. HTTT: Consultancy fees from Janssen-Cilag, AbbVie, Bayer, Novartis and AstraZeneca.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Scheme of treatment until cycle 15 and randomisation of MRD-negative patients. BM, bone marrow; MRD, minimal residual disease; neg, negative; PB, peripheral blood; pos, positive.

Figure 2

Scheme of reinduction treatment of MRD-negative patients after cycle 15 turning MRD positive after treatment cessation. CLL, chronic lymphocytic leukaemia; iwCLL, International Workshop on Chronic Lymphocytic Leukemia; MRD, minimal residual disease.