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

G A Horne; J Stobo; C Kelly; A Mukhopadhyay; A L Latif; J Dixon-Hughes; L McMahon; P Cony-Makhoul; J Byrne; G Smith; S Koschmieder; T H BrÜmmendorf; P Schafhausen; P Gallipoli; F Thomson; W Cong; R E Clark; D Milojkovic; G V Helgason; L Foroni; F E Nicolini; T L Holyoake; M Copland

doi:10.1038/s41375-019-0700-9

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

Standard

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 A; Stobo, J; Kelly, C; Mukhopadhyay, A; Latif, A L; Dixon-Hughes, J; McMahon, L; Cony-Makhoul, P; Byrne, J; Smith, G; Koschmieder, S; BrÜmmendorf, T H; Schafhausen, P; Gallipoli, P; Thomson, F; Cong, W; Clark, R E; Milojkovic, D; Helgason, G V; Foroni, L; Nicolini, F E; Holyoake, T L; Copland, M.

in: LEUKEMIA, Jahrgang 34, Nr. 7, 07.2020, S. 1775-1786.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Horne, GA, Stobo, J, Kelly, C, Mukhopadhyay, A, Latif, AL, Dixon-Hughes, J, McMahon, L, Cony-Makhoul, P, Byrne, J, Smith, G, Koschmieder, S, BrÜmmendorf, TH, Schafhausen, P, Gallipoli, P, Thomson, F, Cong, W, Clark, RE, Milojkovic, D, Helgason, GV, Foroni, L, Nicolini, FE, Holyoake, TL & 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, Jg. 34, Nr. 7, S. 1775-1786. https://doi.org/10.1038/s41375-019-0700-9

APA

Horne, G. A., Stobo, J., Kelly, C., Mukhopadhyay, A., Latif, A. L., Dixon-Hughes, J., McMahon, L., Cony-Makhoul, P., Byrne, J., Smith, G., Koschmieder, S., BrÜmmendorf, T. H., Schafhausen, P., Gallipoli, P., Thomson, F., Cong, W., Clark, R. E., Milojkovic, D., Helgason, G. V., ... 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, 34(7), 1775-1786. https://doi.org/10.1038/s41375-019-0700-9

Vancouver

Horne GA, Stobo J, Kelly C, Mukhopadhyay A, Latif AL, Dixon-Hughes J et al. 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. 2020 Jul;34(7):1775-1786. https://doi.org/10.1038/s41375-019-0700-9

Bibtex

@article{a89ecbb04275408e9bc937cd5cb8ad38,

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 = "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.",

keywords = "Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Cytogenetic Analysis/methods, Female, Follow-Up Studies, Fusion Proteins, bcr-abl/genetics, Humans, Hydroxychloroquine/administration & dosage, Imatinib Mesylate/administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Rate",

author = "Horne, {G A} and J Stobo and C Kelly and A Mukhopadhyay and Latif, {A L} and J Dixon-Hughes and L McMahon and P Cony-Makhoul and J Byrne and G Smith and S Koschmieder and Br{\"U}mmendorf, {T H} and P Schafhausen and P Gallipoli and F Thomson and W Cong and Clark, {R E} and D Milojkovic and Helgason, {G V} and L Foroni and Nicolini, {F E} and Holyoake, {T L} and M Copland",

year = "2020",

month = jul,

doi = "10.1038/s41375-019-0700-9",

language = "English",

volume = "34",

pages = "1775--1786",

journal = "LEUKEMIA",

issn = "0887-6924",

publisher = "NATURE PUBLISHING GROUP",

number = "7",

}

RIS

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, G A

AU - Stobo, J

AU - Kelly, C

AU - Mukhopadhyay, A

AU - Latif, A L

AU - Dixon-Hughes, J

AU - McMahon, L

AU - Cony-Makhoul, P

AU - Byrne, J

AU - Smith, G

AU - Koschmieder, S

AU - BrÜmmendorf, T H

AU - Schafhausen, P

AU - Gallipoli, P

AU - Thomson, F

AU - Cong, W

AU - Clark, R E

AU - Milojkovic, D

AU - Helgason, G V

AU - Foroni, L

AU - Nicolini, F E

AU - Holyoake, T L

AU - Copland, M

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Cytogenetic Analysis/methods

KW - Female

KW - Follow-Up Studies

KW - Fusion Proteins, bcr-abl/genetics

KW - Humans

KW - Hydroxychloroquine/administration & dosage

KW - Imatinib Mesylate/administration & dosage

KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Retrospective Studies

KW - Survival Rate

U2 - 10.1038/s41375-019-0700-9

DO - 10.1038/s41375-019-0700-9

M3 - SCORING: Journal article

C2 - 31925317

VL - 34

SP - 1775

EP - 1786

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 7

ER -