A randomised Phase II trial of Imatinib (IM) versus Hydroxychloroquine (HCQ) and Imatinib (IM) for patients with Chronic Myeloid Leukaemia (CML) in Cytogenetic Response (CyR) with residual disease detectable by quantitative polymerase chain reaction (Q-PCR) - CHOICES-CHlOroquine and Imatinib Combination to Eliminate Stem cells

Phase 1

• Conditions: Chronic Myeloid Leukaemia; MedDRA version: 14.0 Level: PT Classification code 10009013 Term: Chronic myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-014373-41-GB
• Lead Sponsor: HS Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-03-17
• Study Completion: 2017-06-27
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 62

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. Patients must have fusion gene that can be monitored by Q-PCR 4. CML CP patients who have been treated with and tolerated imatinib for more than 1 year, have achieved at least major cytogenetic response and continue to be BCR/ABL+ by Q-PCR. Patients should be receiving a stable dose of imatinib for 6 months prior to study entry 5. Patients must meet the following laboratory criteria: ANC and PLT need to be stable and in the range of ANC =1.5 and platelets = 100 for =2 months Serum albumin >3g/dl AST and ALT =2.5 x upper limit of normal (ULN) Serum bilirubin =1.5 x ULN Serum creatinine =1.5 x ULN or 24-hour creatinine clearance =50 ml/min Serum potassium =LLN 6. ECOG Performance Status of =2
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Patient who have been treated with imatinib <1 year or patients who have changed dose in previous 6 months 2. Impaired cardiac function including any one of the following: Screening ECG with a QTc >450 msec Patients with congenital long QT syndrome History or presence of sustained ventricular tachycardia Any history of ventricular fibrillation or torsades de pointes Congestive heart failure (NY Heart Association class III or IV) Uncontrolled hypertension 3. Patients with severe GI disorder, uncontrolled epilepsy, known G6PD deficiency, known porphyria, moderate or severe psoriasis, known myasthenia 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 study. 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 study. 9. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To provide preliminary evidence that HCQ given in combination with imatinib is more effective than imatinib alone in terms of BCR/ABL levels in CML patients who are in major cytogenetic response with residual BCR/ABL+ cells after at least one year of imatinib treatment. • To determine the safety and tolerability of HCQ given in combination with imatinib in these patients.;Secondary Objective: • To determine whether the introduction of HCQ influences imatinib plasma levels and to confirm that whole blood HCQ levels achieved on a continuous 800mg/day dose in combination with imatinib are in the expected range.;Primary end point(s): The primary study end-point is the proportion of treatment successes” defined as patients who have >0.5 log reductions in their 12 month PCR level of BCR/ABL transcripts from baseline. Patients who withdraw before the 12 month assessment or who have an increase in their imatinib dose prior to the assessment will be classified as treatment failures”.