Condition category
Cancer
Date applied
24/08/2009
Date assigned
19/11/2009
Last edited
16/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Tessa Holyoake

ORCID ID

Contact details

The Paul O’Gorman 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 measures

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

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

http://www.nhsggc.org.uk

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 24/03/2011 the overall trial end date was changed from 01/03/2012 to 31/10/2013.