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
EudraCT/CTIS number 2009-014375-41
ClinicalTrials.gov number NCT01227135
Secondary identifying numbers G0900882
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 O’Gorman Leukaemia Research Centre
Gartnavel General Hospital
Glasgow
G12 0XB
United Kingdom

Study information

Study designRandomised phase II trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA 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 acronymCHOICES - Chloroquine and imatinib combination to eliminate stem cells
Study objectives1. 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) studiedChronic myeloid leukaemia
InterventionImatinib 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Chloroquine, imatinib
Primary outcome measureProportion 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.
Secondary outcome measures1. 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.
Overall study start date01/04/2010
Completion date31/10/2013

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants66
Key inclusion criteria1. 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 criteria1. 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 enrolment01/04/2010
Date of final enrolment31/10/2013

Locations

Countries of recruitment

  • Scotland
  • United Kingdom

Study participating centre

Gartnavel General Hospital
Glasgow
G12 0XB
United Kingdom

Sponsor information

NHS Greater Glasgow and Clyde (UK)
Government

Nathaniel Brittian
R and D Central Office
Tennent Institute
1st Floor
Western Infirmary General
38 Church Street
Glasgow
G11 6NT
United Kingdom

Website http://www.nhsggc.org.uk
ROR logo "ROR" https://ror.org/05kdz4d87

Funders

Funder type

Research council

Medical Research Council (MRC) (UK)
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom

Results and Publications

Intention to publish date01/08/2019
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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

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.