E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
newly diagnosed FLT3 mutated acute myeloid leukemia |
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E.1.1.1 | Medical condition in easily understood language |
newly diagnosed acute myeloid leukemia |
|
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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To determine if the addition of midostaurin to daunorubicin/cytarabine induction, high-dose cytarabine consolidation, and continuation therapy improves overall survival (OS) in both the mutant FLT3-ITD and FLT3-TKD AML patients. |
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E.2.2 | Secondary objectives of the trial |
Key: To compare the event-free survival (EFS) between the two treatment groups.
Other:-To compare OS between the two treatment groups using an analysis in which patients who receive a SCT are censored at the time of transplant.
-To compare the CR rate between the two treatment groups.
-To compare the DFS of the two treatment groups.
-To compare the DFS rate one year after completion of the continuation phase of the two groups.
-To assess the toxicity of the experimental combination.
-To describe the interaction between treatment outcome and pretreatment characteristics such as age, performance status, WBC count, morphology, cytogenetics, and molecular and pharmacodynamic features.
-To assess the population pharmacokinetics (popPK) of midostaurin and its two major metabolites, CGP52421 and CGP62221.The potential association(s) between PK exposure and FLT3 status, OS, EFS and clinical response will be explored.
-To assess and compare the SCT rate between the two treatment groups. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Unequivocal diagnosis of AML (> 20% blasts in the bone marrow based on the WHO classification, excluding M3 (acute promyelocytic leukemia)
- Documented FLT3 mutation
- Age >18 and < 60 years
- No prior chemotherapy for leukemia or myelodysplasia with few exception listed (see protocol section 4) |
|
E.4 | Principal exclusion criteria |
- Patients who have developed therapy related AML after prior RT or chemotherapy for another disorder or cancer
- Patients with symptomatic congestive heart failure
- Total bilirubin >= 2.5x upper limit of normal
- Pregnant or nursing patients |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary analysis with a cutoff date of April 1, 2015 after a minimum follow up of approximately 3.5 years after the randomization of the last patient (October 15th 2011).
A supportive (final) analysis at the end of the trial when the 10 year post-randomization follow up period has been completed for all patients, or when 509 events are observed, whichever occurs first. |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoint:
- event free survival
Other secondary endpoints:
- overall survival (OS) where patients who receive a stem cell transplant (SCT) are censored at the time of the transplant
- complete response (CR) rate in the remission induction stage of the study
- disease free survival (DFS)
- DFS rate one year after completing the planned continuation phase
- SCT rates |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Primary analysis with a cutoff date of April 1, 2015 after a minimum follow up of approximately 3.5 years after the randomization of the last patient (October 15th 2011).
A supportive (final) analysis at the end of the trial when the 10 year post-randomization follow up period has been completed for all patients, or when 509 events are observed, whichever occurs 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 | 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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 114 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Netherlands |
Slovakia |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Last visit of the last patient |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |