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)
- Conditions
- Chronic myeloid leukaemiaCancerMyeloid leukaemia
- Registration Number
- ISRCTN61568166
- Lead Sponsor
- HS Greater Glasgow and Clyde (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 66
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 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.<br><br> All analyses will be conducted on an intention to treat basis.<br>
- Secondary Outcome Measures
Name Time Method <br> 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.<br> 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.<br> 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.<br><br> 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.<br><br> Adverse events will also be recorded throughout the trial.<br>