E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced systemic mastocytosis carrying the D816V KIT mutation (or different exon 17 KIT mutations). |
Mastocitosis sistémica de mal pronóstico con la mutación D816V u otras mutaciones en el exón 17 de KIT. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced systemic mastocytosis carrying the D816V KIT mutation (or different exon 17 KIT mutations). |
Mastocitosis sistémica de mal pronóstico con la mutación D816V u otras mutaciones en el exón 17 de KIT. |
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E.1.1.2 | Therapeutic area | Not possible to specify |
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 analyze the efficacy and safety of the combined use of cladribine plus peginterpheron alfa-2a in patients with advanced systemic mastocytosis. |
Analizar la eficacia del uso combinado de cladribina y peginterferón alfa-2a en pacientes con mastocitosis sistémica de mal pronóstico. |
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E.2.2 | Secondary objectives of the trial |
To analyze the safety of the combined use of cladribine plus peginterpheron alfa-2a in patients with advanced systemic mastocytosis. |
Analizar la seguridad del uso combinado de cladribina y peginterferón alfa-2a en pacientes con mastocitosis sistémica de mal pronóstico. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age older than 18 years. Diagnosis of advanced systemic mastocytosis (aggressive systemic mastocytosis or proggressing systemic mastocytosis) with D816V or other exon 17 KIT mutations. ECOG ≤ 3. Signed informed consent. |
Edad igual o mayor a 18 años. Diagnóstico de mastocitosis sistémica de mal pronóstico (mastocitosis sistémica agresiva o en progresión) con la mutación D816V u otras mutaciones en el exón 17 de KIT. ECOG ≤ 3. Firma del consentimiento informado. |
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E.4 | Principal exclusion criteria |
Impaired liver function (total bilirubin ≥ 2.0 mg/dl, AST or ALT > 3 x upper limit of normal) not related to mastocytosis. Impaired renal function (creatinine ≥ 2.0 mg/dL) not related to mastocytosis. Grade III-IV cytopenias not related to mastocytosis. Severe cardiopathy (grade III/IV of NYHA, or left ventricular ejection fraction < 50%). Pregnancy or breastfeeding. Female patients who do not use contraceptive methods. |
Alteración de la función hepática (bilirrubina total ≥ 2.0 mg/dl, GOT o GPT> 3 veces el límite superior de la normalidad) no relacionada con la mastocitosis. Alteración de la función renal (creatinina ≥ 2.0 mg/dL) no relacionada con la mastocitosis. Citopenias grado III-IV no relacionadas con la mastocitosis. Cardiopatía severa (grado III/IV de la NYHA o fracción de eyección del ventrículo izquierdo < 50%). Embarazo o lactancia. Mujeres en edad fértil que no usen métodos anticonceptivos fiables.
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the effect of therapy on bone marrow mast cell infiltration. |
Evaluar el efecto del tratamiento sobre la infiltración mastocitaria en médula ósea. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 and 6 months. |
3 y 6 meses. |
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E.5.2 | Secondary end point(s) |
To determine the effect of therapy on serum tryptase levels and other altered peripheral blood parameters due to mastocytosis. To evaluate the effect of therapy on mast cell-mediator release symptoms: pruritus, flushing, gastrointestinal symptoms or anaphylaxis). To determine the safety of combined therapy with cladribine plus pegylated interpheron alpha-2a. To evaluate the effect of therapy on mastocytosis skin lesions. To evaluate the effect of therapy on mastocytosis-related organomegalies. To evaluate the effect of therapy on mastocytosis-related bone alterations.
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determinar el efecto del tratamiento sobre los niveles de triptasa sérica y otras alteraciones analíticas relacionadas con la mastocitosis. Evaluar el efecto del tratamiento sobre los síntomas de liberación de mediadores mastocitarios: picor, flushing, síntomas gastrointestinales o anafilaxia. Determinar la seguridad del tratamiento combinado con cladribina y peginterferon alfa-2a. Evaluar el efecto del tratamiento sobre las lesiones cutáneas de la mastocitosis. Evaluar el efecto del tratamiento sobre las organomegalias relacionadas con la mastocitosis. Evaluar el efecto del tratamiento sobre las alteraciones óseas relacionadas con la mastocitosis. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months for every endpoint. |
6 meses para cada objetivo. |
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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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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LVLS |
Última visita de último sujeto a estudio. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |