E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic myeloproliferative diseases |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028578 |
|
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 evaluate efficacy and safety of ITF 2357 in the treatment of patients with JAK2 V617F positive myeloproliferative diseases (PV, ET, MF). Efficacy will be evaluated by ad hoc haematological and clinical criteria for PV and ET, and by internationally established response criteria for MF. Safety will be evaluated by number of subjects experiencing an AE, type, frequency, severity, timing and relatedness of AEs (including changes in vital signs and clinical laboratory results |
|
E.2.2 | Secondary objectives of the trial |
to evaluate the JAK2 mutated allele burden by quantitative RT PCR |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Signed Informed Consent Form Male or female, age ≥ 18 years Confirmed diagnosis of PV/ET/MF according to the revised WHO criteria JAK-2 V617F positivity In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. young patients) or when refractoriness to the drug is documented |
|
E.4 | Principal exclusion criteria |
Active bacterial or fungal infection requiring antimicrobial treatment on Day 1 Patients of childbearing potential without a negative pregnancy test prior to initiation of the study drug Pregnancy or lactation A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazetts correction formula see appendix G for the formula) The use of concomitant medications that prolong the QT/QTc interval (see appendix F for full list) Concomitant acute coronary syndromes; uncontrolled hypertension New York Heart Association (NYHA) Grade II or greater congestive heart failure History of any cardiac arrhythmia requiring medication (irrespective of its severity) A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Active EBV infection (i.e. positive serology IgM) Known HIV infection Active hepatitis B and/or C infection History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications ECOG performance status 3 or greater Platelets count <100x109/L within 14 days before enrolment Absolute neutrophil count <1.2x109/L within 14 days before enrolment Percentage of blast cells in peripheral blood >10% within 14 days before enrolment Serum creatinine >2xULN Total serum bilirubin >1.5xULN Serum AST/ALT > 3xULN Interferon alpha within 14 days before enrolment Hydroxyurea within 14 days before enrolment Anagrelide within 7 days before enrolment Any other investigational drug within 28 days before enrolment |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of Objective Responses (OR) The number of subjects experiencing an adverse event |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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.8.5 | 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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |