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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

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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, Gillian; Stobo, Jon; Kelly, Caroline; Mukhopadhyay, Arunima; Latif, Anne; Dixon, Judith; McMahon, Lynn; Cony-Makhoul, P; Byrne, Jenny; Smith, Graeme; Koschmieder, schafhausen; BrÜmmendorf , T; Schafhausen, P; Gallipoli, P; Thomson, Fiona; Cong, Wenjuan; Clark, R; Milojkovic, Dragana; Helgason, Vignir; Foroni, Letizia; NICOLINI, Franck-Emmanuel ; Holyoake, Tessa; Copland, Mhairi.

In: Leukemia, 10.01.2020.

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Horne, G, Stobo, J, Kelly, C, Mukhopadhyay, A, Latif, A, Dixon, J, McMahon, L, Cony-Makhoul, P, Byrne, J, Smith, G, Koschmieder, S, BrÜmmendorf , T, Schafhausen, P, Gallipoli, P, Thomson, F, Cong, W, Clark, R, Milojkovic, D, Helgason, V, Foroni, L, NICOLINI, F-E, Holyoake, T & Copland, M 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. https://doi.org/10.1038/s41375-019-0700-9

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Horne, Gillian ; Stobo, Jon ; Kelly, Caroline ; Mukhopadhyay, Arunima ; Latif, Anne ; Dixon, Judith ; McMahon, Lynn ; Cony-Makhoul, P ; Byrne, Jenny ; Smith, Graeme ; Koschmieder, schafhausen ; BrÜmmendorf , T ; Schafhausen, P ; Gallipoli, P ; Thomson, Fiona ; Cong, Wenjuan ; Clark, R ; Milojkovic, Dragana ; Helgason, Vignir ; Foroni, Letizia ; NICOLINI, Franck-Emmanuel ; Holyoake, Tessa ; Copland, Mhairi. / 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. In: Leukemia. 2020.

Bibtex

@article{83ab3cf0a2d241c5b2d18f989bc89676,
title = "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",
abstract = "Abstract: 1 In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are 2 responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and 3 Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed 4 to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared to IM alone in 5 CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two 6 patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end-point, 7 defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end-8 points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, 9 comparison of IM levels, and achievement of blood HCQ levels >2000ng/ml. At 12 months, there was no 10 difference in ‘success’ rate (p=0.58); MMR was achieved in 80{\%} (IM) vs 92{\%} (IM/HCQ) (p=0.21). At 24 11 months, the ‘success’ rate was 20.8{\%} higher with IM/HCQ (p=0.059). No patients progressed. 12 Seventeen adverse events, including four serious adverse reactions, were reported; diarrhoea occurred 13 more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR 14 levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.",
author = "Gillian Horne and Jon Stobo and Caroline Kelly and Arunima Mukhopadhyay and Anne Latif and Judith Dixon and Lynn McMahon and P Cony-Makhoul and Jenny Byrne and Graeme Smith and schafhausen Koschmieder and T Br{\"U}mmendorf and P Schafhausen and P Gallipoli and Fiona Thomson and Wenjuan Cong and R Clark and Dragana Milojkovic and Vignir Helgason and Letizia Foroni and Franck-Emmanuel NICOLINI and Tessa Holyoake and Mhairi Copland",
year = "2020",
month = "1",
day = "10",
doi = "10.1038/s41375-019-0700-9",
language = "English",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Springer Nature",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - 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

AU - Horne, Gillian

AU - Stobo, Jon

AU - Kelly, Caroline

AU - Mukhopadhyay, Arunima

AU - Latif, Anne

AU - Dixon, Judith

AU - McMahon, Lynn

AU - Cony-Makhoul, P

AU - Byrne, Jenny

AU - Smith, Graeme

AU - Koschmieder, schafhausen

AU - BrÜmmendorf , T

AU - Schafhausen, P

AU - Gallipoli, P

AU - Thomson, Fiona

AU - Cong, Wenjuan

AU - Clark, R

AU - Milojkovic, Dragana

AU - Helgason, Vignir

AU - Foroni, Letizia

AU - NICOLINI, Franck-Emmanuel

AU - Holyoake, Tessa

AU - Copland, Mhairi

PY - 2020/1/10

Y1 - 2020/1/10

N2 - Abstract: 1 In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are 2 responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and 3 Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed 4 to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared to IM alone in 5 CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two 6 patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end-point, 7 defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end-8 points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, 9 comparison of IM levels, and achievement of blood HCQ levels >2000ng/ml. At 12 months, there was no 10 difference in ‘success’ rate (p=0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p=0.21). At 24 11 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p=0.059). No patients progressed. 12 Seventeen adverse events, including four serious adverse reactions, were reported; diarrhoea occurred 13 more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR 14 levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.

AB - Abstract: 1 In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are 2 responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and 3 Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed 4 to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared to IM alone in 5 CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two 6 patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end-point, 7 defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end-8 points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, 9 comparison of IM levels, and achievement of blood HCQ levels >2000ng/ml. At 12 months, there was no 10 difference in ‘success’ rate (p=0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p=0.21). At 24 11 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p=0.059). No patients progressed. 12 Seventeen adverse events, including four serious adverse reactions, were reported; diarrhoea occurred 13 more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR 14 levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.

U2 - 10.1038/s41375-019-0700-9

DO - 10.1038/s41375-019-0700-9

M3 - Article

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -