Imatinib (IM) versus hydroxychloroquine (HCQ) and IM for patients with chronic myeloid leukaemia (CML) in cytogenetic response (CyR) with residual disease detectable by quantitative polymerase chain reaction (Q-PCR)

ISRCTN	ISRCTN61568166
DOI	https://doi.org/10.1186/ISRCTN61568166
ClinicalTrials.gov (NCT)	NCT01227135
Clinical Trials Information System (CTIS)	2009-014375-41
Protocol serial number	G0900882
Sponsor	NHS Greater Glasgow and Clyde (UK)
Funder	Medical Research Council (MRC) (UK)

Submission date: 24/08/2009
Registration date: 19/11/2009
Last edited: 23/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-hydroxychloroquine-with-imatinib-for-cml-choices

(Updated 21/05/2019, previously: http://www.cancerhelp.org.uk/trials/a-trial-hydroxychloroquine-with-imatinib-for-cml-choices)

Contact information

Prof Tessa Holyoake
Scientific

The Paul OGorman Leukaemia Research Centre
Gartnavel General Hospital
Glasgow
G12 0XB
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised phase II trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised Phase II trial of Imatinib (IM) versus Hydroxychloroquine (HCQ) and IM for patients with Chronic Myeloid Leukaemia (CML) in Cytogenetic Response (CyR) with residual disease detectable by quantitative polymer chain reaction (Q-PCR)
Study acronym	CHOICES - Chloroquine and imatinib combination to eliminate stem cells
Study objectives	1. To provide preliminary evidence that hydroxychloroquine (HCQ) given in combination with imatinib is more effective than imatinib alone in terms of BCR/ABL levels in chronic myeloid leukaemia (CML) patients who are in moderate cytogenetic response (MCyR) with residual BCR/ABL+ cells after at least one year of imatinib treatment. 2. To determine the safety and tolerability of HCQ given in combination with imatinib in these patients.
Ethics approval(s)	West of Scotland REC 1, 01/12/2009, REC ref: 09/S0703/112
Health condition(s) or problem(s) studied	Chronic myeloid leukaemia
Intervention	Imatinib alone arm: Patients will continue to receive the once-daily dose of imatinib (oral) that they were receiving prior to entry in the trial. This is the control arm of the study. Imatinib + HCQ arm: Patients will continue to receive the once-daily dose of imatinib (oral) that they were receiving prior to entry in the trial. In addition they will receive HCQ (oral), 400 mg twice-daily. This is the interventional treatment under study. Total duration of interventions: 12 months Total duration of follow-up: to be confirmed as of 24/08/2009
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Chloroquine, imatinib
Primary outcome measure(s)	Proportion of treatment "successes" defined as patients who have ≥0.5 log reductions in their 12 month PCR level from baseline. Patients who withdraw before the 12 month assessment or who have an increase in their IM dose prior to the assessment will be classified as treatment "failures". All analyses will be conducted on an intention to treat basis.
Key secondary outcome measure(s)	1. The proportion of treatment "successes" at 24 months. Again patients who withdraw or increase their IM dose prior to 24 months will be classified as treatment "failures". 2. Molecular response at 12 and 24 months (classified as Complete, Major and No response). Patients who withdraw or increase their IM dose prior to the assessment will be classified as non-responders. 3. The proportion of patients with progression at 12 and 24 months. Patients who withdraw or increase their IM dose prior to the assessment will be classified as progressing. All analyses will be conducted on an intention to treat basis. The comparisons between the study arms of "success", molecular response rates and progression rates will use Fisher's exact test. Adverse events will also be recorded throughout the trial.
Completion date	31/10/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	66
Key inclusion criteria	1. Male or female patients aged ≥18 years old 2. Ability to provide written informed consent prior to participation in the study and any related procedures being performed 3. CML Chronic phase (CP) patients who have been treated with and tolerated imatinib for 1-3 years, have achieved at least MCyR and continue to be BCR/ABL+ by quantitative polymerase chain reaction (Q-PCR). Patients should be receiving a stable dose of imatinib for 6 months prior to study entry. 4. Patients must meet the following laboratory criteria: 4.1. Absolute neutrophil count (ANC) and platelet (PLT) need to be stable and in the normal range for ≥2 months 4.2. Serum albumin >3 g/dl 4.3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) 4.4. Serum bilirubin ≤1.5 x ULN 4.5. Serum creatinine ≤1.5 x ULN or 24-hour creatinine clearance >=50 ml/min 4.6. Serum potassium ≥ Lower limit of normal (LLN) 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
Key exclusion criteria	1. Patient who have been treated with imatinib <1 or >3 years or patients who have changed dose in previous 6 months 2. Impaired cardiac function including any one of the following: 2.1. Screening electrocardiogram with a QTc >450 msec 2.2. Patients with congenital long QT syndrome 2.3. History or presence of sustained ventricular tachycardia 2.4. Any history of ventricular fibrillation or torsades de pointes 2.5. Congestive heart failure (New York Heart Association class III or IV) 2.6. Uncontrolled hypertension 3. Patients with severe gastrointestinal (GI) disorder, uncontrolled epilepsy, known G6PD deficiency, known porphyria, moderate or severe psoriasis, known myaesthenia gravis or other concurrent severe and/or uncontrolled medical conditions 4. Patients who have received chemotherapy, any investigational drug or undergone major surgery <4 weeks prior to starting study drug or who have not recovered from side effects of such therapy 5. Concomitant use of any other anti-cancer therapy or radiation therapy 6. Female patients who are pregnant or breast feeding or patients of reproductive potential not willing to use a double method of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment 7. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral HCQ 8. Male patients whose sexual partners are WOCBP not willing to use a double method of contraception including condom during the study and 3 months after the end of treatment 9. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
Date of first enrolment	01/04/2010
Date of final enrolment	31/10/2013

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

Gartnavel General Hospital

Glasgow
G12 0XB
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

23/05/2019: The intention to publish date was added.
21/05/2019: No publications found, verifying study status with principal investigator. Updated link to plain English summary.
29/03/2018: No publications found, verifying study status with principal investigator.
On 24/03/2011 the overall trial end date was changed from 01/03/2012 to 31/10/2013.