E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10042949 |
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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 |
Assessment of the clinical response rate in patients with a diagnosis of systemic mastocytosis in terms of both B/C findings and mediator-related symptoms |
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E.2.2 | Secondary objectives of the trial |
1)To assess the duration of response (DOR) and progression free survival (PFS); 2)to evaluate the changes in specific biological markers and molecular changes; 3) to evaluate the safety and toxicity of repeated oral administration of dasatinib. Additional information derived from post-hoc analysis will be: 1) evaluation of efficacy of dasatinib in patients carrying the D816V mutation as compared to that in patients with other mutations or with wild-type KIT and 2) development of an ex vivo system to evaluate therapeutic response to dasatinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) A diagnosis of systemic mastocytosis, according to the WHO criteria; 2) A classification of mastocytosis as either aggressive (presence of C-findings) or smouldering/indolent (presence of B-findings) with severe clinical signs or symptoms unresponsive to antimediator treatment; patients with mastocytosis associated with hematologic non mast cell disease (AHNMD) will be included if the two disorders need to be treated independently, as indicated by the Consensus Guidelines 3) Age >18 years old. Fertile men and women must agree to use a medically acceptable form of contraception during the study; 4) A preserved liver and kidney function as assessed by: a) total bilirubin not exceeding 2.0 times the institutional upper limit of normal (ULN); b) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) not exceeding 2.5 times ULN; c) serum creatinine not exceeding 2.0 times ULN. |
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E.4 | Principal exclusion criteria |
1) Pregnancy or breast feeding; 2) Uncontrolled CNS involvement by mastocytosis or other medical disorder that would impair the ability of the subject to receive cytoreductive therapy; 3) Uncontrolled or active significant cardiovascular disease; 4) An altered mental status that would prevent understanding or rendering of informed consent; 5) Clinically significant bleeding from the GI tract within the last 2 months; 6) Current treatment with prednisone at dose >15 mg/day; 7) Current treatment with cytoreductive drug (IFN, 2-CdA or imatinib). Patients can be enrolled in the study if this treatment has been discontinued at least 1 month prior of enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of the clinical response rate in patients with a diagnosis of systemic mastocytosis in terms of both clincal findings related to organ infiltration by mast cells and mediator-related symptoms |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
valutazione delle modifiche in specifici markers biologici e mutazioni molecolari |
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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 | Yes |
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 | 12 |
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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Ultima visita dell`ultimo paziente |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |