E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aggressive Systemic Mastocytosis or Mast Cell Leukemia +/- an Associated Hematological Clonal Non-Mast Cell Lineage Disease |
|
E.1.1.1 | Medical condition in easily understood language |
Aggressive Systemic Mastocytosis or Mast Cell 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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056453 |
E.1.2 | Term | Aggressive systemic mastocytosis |
E.1.2 | System Organ Class | 100000004851 |
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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 the efficacy of midostaurin in patients with ASM or MCL with or without AHNMD when administered orally at a dose of 100 mg b.i.d. continuously for 6 cycles (of 4 weeks each) as measured by overall response rate |
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E.2.2 | Secondary objectives of the trial |
To evaluate:
- duration of response
- time to response
- overall survival
- progression free survival
Safety and tolerability of midostaturin
to characterise KIT mutational status in the SM compartment and if applicable also in the AHNMD compartment of the disease at baseline, after 6 cycles of therapy and at end of study (EOS) and explore potential association with efficacy outcomes.
- To evaluate the histopathologic response based on mast cell infiltration in the bone marrow (BM) and changes in serum tryptase levels as surrogate marker for histopathologic response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients aged 18 and over
- ECOG performance status of 0-3
- life expectancy > 12 weeks
- ECG QTcF interval ≤ 450 ms
-meeting following lab values:
AST and ALT ≤ 2.5 x ULN, if caused by ASM/MCL: ≤ 5 x ULN
Serum Bilirubin ≤ 1.5 ULN, if related to ASM/MCL: ≤3x ULN
Serum Creatinine ≤ 2.0 mg/dl diagnosed with ASM or MCL according to WHO criteria for SM plus for ASM or MCL |
|
E.4 | Principal exclusion criteria |
- patients unwilling or unable to comply with the protocol
- any other concurrent severe known disease and/or severe uncontrolled medical condiction which could compromise participation in the study
- patients with cardiovascular disease including congestive heart failure grade III or IV according to the NYHA classification, left ventricular ejection fraction of <50%, myocardial infection within previous 6 months and poorly controlled hypertension
- confirmed diagnosis of HIV infection or active viral hepatitis
- female patients who are pregnant or breast feeding or adults of reproductive
potential not employing a highly effective method of birth control
- patients presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs (other than midostaurin)
- patients who have demonstrated relapse to 3 or more prior regimens of SM treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After continuous treatment of 6 cycles (of 4 weeks each), response must be confirmed 8 weeks apart. |
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E.5.2 | Secondary end point(s) |
- duration of response
- event free survival
- time to response
- overall survival
-safety
- histopathologic response |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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 | 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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
|
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
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |