E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV MF) or Post essential thrombocythemia myelofibrosis (PET-MF) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
to collect additional safety of INC424 in patients with PMF, PPV MF, or PET MF, who have either received prior treatment with commercially available agents or never received treatment |
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E.2.2 | Secondary objectives of the trial |
To document the best overall response rate to INC424 in patients with PMF, PPV MF , or PET MF as evaluated by the investigator
To collect quality of life (QoL) endpoints
To document medical resource utilization |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. patient must give written informed consent according to local guideliens prior to any screening procedure
2. patients must not be eligible for another ongoing INC424 clinical trial
3. male or female patients aged >18 years of age
4. patients must be diagnosed with PMF, PPv mf or PET MF according to the WHO citeria 2008
5. PMF patients requiruing therapy must be classified as high risk or intermediate risk level 2 or intermediate risk level 1 with enlarged spleen
6. patients with intermediate-1 and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion
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E.4 | Principal exclusion criteria |
1. Patients eligible for hematopoietic stem cell transplantation
2. Patients with a history of malignancy in the past 3 years, except for treated early stage squamous or basal cell carcinoma in situ
3. patients undergoing treatment with hematopoietic growth factor receptor agonists, granulocyte colony stimulant factor at nay time within 2 weeks prior to screening or 4 weeks prior to baseline
4. Patients currently participating in COMFORT-I and COMFORT -II trials
5.Patients receiving any medications listed in the "prohibited medications" listing
6. Impairment of GI function or GI disease that may alter the absorption of INC424
7. Patients with cardiac disease which my jeopardize the safety of the patient
8. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal fibrillation or recent myocardial infarction or acute coronary syndrome
9. Patients with clinically significant infections (for further details see protocol)
10. Patients with known active hepatitis a, B, C or who are HIV -positive
11. Patients with coagulation parameters
12.Pregnant or nursing women |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety:
Clinical and laboratory parameters will be collected to evaluate study drug safety and toxicity.
Safety and tolerability will be collected by monitoring the frequency, duration and severity of all grade adverse events (AEs) by CTCAE v.3.0, performing physical exams (PE), and evaluating changes in vital signs (VS), ECOG performance status (PS), ECGs and serum chemistry and hematology results.
Grade 3 and 4 AEsm, Serious Adverse Events (SAEs).
Frequency of dose interruptions and discontinuations due to AEs.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly for the first 3 months, then every 3 months and at study discontinuation |
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E.5.2 | Secondary end point(s) |
Quality of life:
Change in ECOG PS from baseline
Change in FACT-Lym
Change in Functional Assessment of Chronic Illness Therapy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Monthly for the first 3 months, then every 3 months and at study discontinuation |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
Colombia |
Korea, Republic of |
Lebanon |
Mexico |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Switzerland |
Taiwan |
Venezuela, Bolivarian Republic of |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |