Plain English Summary
http://www.cancerhelp.org.uk/trials/a-trial-hydroxychloroquine-with-imatinib-for-cml-choices
Trial website
Contact information
Type
Scientific
Primary contact
Prof Tessa Holyoake
ORCID ID
Contact details
The Paul OGorman Leukaemia Research Centre
Gartnavel General Hospital
Glasgow
G12 0XB
United Kingdom
+44 (0)141 301 7881
t.holyoake@clinmed.gla.ac.uk
Additional identifiers
EudraCT number
2009-014375-41
ClinicalTrials.gov number
NCT01227135
Protocol/serial number
G0900882
Study information
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)
Acronym
CHOICES - Chloroquine and imatinib combination to eliminate stem cells
Study hypothesis
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
West of Scotland REC 1, 01/12/2009, REC ref: 09/S0703/112
Study design
Randomised phase II trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
Chloroquine, imatinib
Primary outcome measure
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.
Secondary outcome measures
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.
Overall trial start date
01/04/2010
Overall trial end date
31/10/2013
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
66
Participant 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
Recruitment start date
01/04/2010
Recruitment end date
31/10/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Gartnavel General Hospital
Glasgow
G12 0XB
United Kingdom
Sponsor information
Organisation
NHS Greater Glasgow and Clyde (UK)
Sponsor details
Nathaniel Brittian
R and D Central Office
Tennent Institute
1st Floor
Western Infirmary General
38 Church Street
Glasgow
G11 6NT
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (MRC) (UK)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list