E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myeloid Leukaemia |
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E.1.1.1 | Medical condition in easily understood language |
Chronisch myeloische Leukämie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009013 |
E.1.2 | Term | Chronic myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- 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 an tolerability of HCQ given in combination with imatinib in these patients. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 study related procedures being performed. 3. Patient must have a fusion gene that can be monitored by Q-PCR 4. CML Chronic phase (CP) patients who have been treated with and tolerated Imatinib for at least 12 Months, have achieved at least MCyR 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 Platelets need to be stable and in the range of ANC > 1.5 and platelets > 100 for ≥2 months • Serum albumin >3g/dl • AST and/or 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 ≥ lower limit of normal (LLN) with or without replacement therapy 6. ECOG Performance Status of ≤2 |
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E.4 | Principal exclusion criteria |
1. Patient who have been treated with Imatinib <12 months 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 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 study entry or who have not recovered from side effects of such therapy. 5. Concomitant use of any other anti-cancer therapy or radiation therapy. 6. Patients who have a pre-exisiting maculopathy of the eye. 7. 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 the study treatment. (Patients should continue with standard contraceptive precautions beyond the study period as per Imatinib). 8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral HCQ. 9. 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. (Patients should continue with standard contraceptive precautions beyond the study period as per Imatinib). 10. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent. |
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E.5 End points |
E.5.1 | 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 BCR/ABL levels as measured by quantitative polymerase chain reaction (Q-PCR). 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”. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 Months after treatment with Hydroxychloroquine and Imatinib |
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E.5.2 | Secondary end point(s) |
- 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". - Molecular response at 12 and 24 months (classified as Complete, Major and No response– see section on response criteria for definition). Patients who withdraw or increase their IM dose prior to the assessment will be classified as non-responders. - The proportion of patients with progression at 12 and 24 months (see section on disease progression for definition). Patients who withdraw or increase Imatinib dose prior to the assessment will be classified as progressing. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 and 24 Months after treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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12 months after treatment or appearence of AEs. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |