A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease

Horne, G. et al. (2020) A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease. Leukemia, 34(7), pp. 1775-1786. (doi: 10.1038/s41375-019-0700-9) (PMID:31925317)

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Abstract

In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in ‘success’ rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Latif, Dr Anne-Louise and Mukhopadhyay, Dr Arunima and Horne, Dr Gillian and Kelly, Mrs Caroline and Stobo, Mr Jon and Copland, Professor Mhairi and Holyoake, Professor Tessa and McMahon, Mrs Lynn and Thomson, Dr Fiona and Cong, Dr Wenjuan
Authors: Horne, G., Stobo, J., Kelly, C., Mukhopadhyay, A., Latif, A.-L., Dixon-Hughes, J., McMahon, L., Cony-Makhoul, P., Byrne, J., Smith, G., Koschmeider, S., Brümmendorf, T.H., Schafhausen, P., Gallipoli, P., Thomson, F., Cong, W., Clark, R. E., Milojkovic, D., Helgason, G. V., Foroni, L., Nicoloni, F. E., Holyoake, T. L., and Copland, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Leukemia
Publisher:Springer Nature
ISSN:0887-6924
ISSN (Online):1476-5551
Published Online:10 January 2020
Copyright Holders:Copyright © 2020 The Authors, under exclusive licence to Springer Nature Limited
First Published:First published in Leukemia 34(7):1775–1786
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190200A randomised Phase II trial of Imatinib (IM) versus hydroxychloroquine (HCQ) with IM for patients with chronic myeloid leukaemia (CML) in cytogenic response (CyR.Tessa HolyoakeMedical Research Council (MRC)G0900882CS - Paul O'Gorman Leukaemia Research Centre
163632Development of a flow cytometry service within the Paul O'Gorman Leukaemia Research CentreAlison MichieThe Kay Kendall Leukaemia Fund (KENDALL)KKL501CS - Paul O'Gorman Leukaemia Research Centre