E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ph positive (Ph+)/Bcr-Abl positive Acute Lymphoblastic Leukemia (ALL) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000844 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the trial is to evaluate the therapeutic effects of NIL and IM given in turn (in rotation) in terms of Disease-Free Survival (DFS) at 24 weeks (after 4 courses of treatment). |
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E.2.2 | Secondary objectives of the trial |
1. Complete Hematological Response (CHR) rate at 6, 12 and 24 weeks 2. Complete Cytogenetic Response (CCgR) rate at 6, 12 and 24 weeks, and duration of CCgR 3. Complete molecular response (CMR) rate at 12 and 24 weeks, and duration of CMolR 4. Type and number of BCR-ABL kinase domain mutations developing during and after the study 5. Relationship between response, biomarkers and gene expression profile (GEP) 6. Event-free survival (EFS) and Overall Survival (OS) 7. Side effects, adverse events (AE) and serious AE (SAE) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with previously untreated Ph+ and/or BCR/ABL + ALL: o age 60 years old or o age > 18 years old, but unfit for program of intensive therapy and allogeneic SCT 2. Written informed consent prior to any study procedures being performed 3. Effective contraception |
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E.4 | Principal exclusion criteria |
1. Impaired cardiac function, including LVEF < 45% as determined by MUGA scan or echocardiogram, uncontrolled congestive heart failure, uncontrolled hypertension 2. History of myocardial infarction within 3 months, or uncontrolled angina pectoris. 3. Significant electric heart abnormalities, including history or presence of significant ventricular or atrial tachyarrhythmias, congenital long QT syndrome and/or QTc > 450 msec on screening ECG (using the QTcF formula) 4. WHO performance status _ 50% (Karnofsky) or _ 3 (ECOG) 5. History of acute (within one year) or chronic pancreatitis. 6. Active HBV or HCV hepatitis, or AST/ALT more than 5 times ULN or bilirubine more than 5 time ULN or INR>1.5 7. Creatinine level >2.5mg/dl or VFG< 2ml/min or proteinuria >5g/day 8. Impairment of gastrointestinal (GI) function, or a GI disease that may significantly alter the absorption of study drugs (e.g., severe malabsorption syndrome, or extended small bowel resection) 9. Patients who are currently receiving treatment with any of the medications listed in Appendix D if the medications cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix D have the potential to prolong QT. 10. Patients who have received any investigational drug _ 4 weeks. 11. Patients who have undergone major surgery _ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. 12. Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of imatinib and nilotinib). Post menopausal women must be amenorrhoic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs. 13. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention. 14. Patients unwilling or unable to comply with the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the Disease-Free Survival (DFS) at 24 weeks (after 4 courses of treatment), defined as the time from the date of 1st CHR to loss of CHR or CCyR, whichever comes first. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 34 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 6 |