E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myelofibrosis |
Mielofibrosis |
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E.1.1.1 | Medical condition in easily understood language |
Bone marrow disorder that disrupts body's normal production of blood cells. The result is extensive scarring in bone marrow, leading to severe anemia, weakness, fatigue and an enlarged spleen. |
Trastorno de la médula ósea que interrumpe la producción normal de células sanguíneas. Provocando cicatrización extensa en la médula ósea, produciendo anemia severa, debilidad, fatiga, bazo agrandado. |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028537 |
E.1.2 | Term | Myelofibrosis |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Evaluate the effect of navitoclax alone or in combination with ruxolitinib on spleen volume |
Evaluar el efecto de navitoclax solo o en combinación con ruxolitinib en el volumen esplénico |
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E.2.2 | Secondary objectives of the trial |
- To assess the effect of navitoclax alone or in combination with ruxolitinib on total symptom score (TSS) as assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0 diary - To evaluate the effect of navitoclax alone or in combination with ruxolitinib on bone marrow fibrosis - To determine the overall response rate (ORR = sum of rates of complete remission [CR] + partial remission [PR]) associated with navitoclax alone or in combination with ruxolitinib - To determine the rate of anemia response associated with navitoclax alone or in combination with ruxolitinib - To describe the safety profile and PK profile observed with navitoclax alone or in combination with ruxolitinib |
•Evaluar el efecto de navitoclax solo o en combinación con ruxolitinib en la puntuación total de síntomas (TSS) evaluada mediante el diario del Formulario de evaluación de los síntomas de mielofibrosis (MFSAF), versión 4.0. •Evaluar el efecto de navitoclax solo o en combinación con ruxolitinib en la fibrosis de la médula ósea •Determinar la tasa de respuestas globales (TRG = suma de las tasas de remisión completa [RC] + remisión parcial [RP]) obtenida con navitoclax solo o en combinación con ruxolitinib. •Determinar la tasa de respuestas de la anemia obtenida con navitoclax solo o en combinación con ruxolitinib •Describir el perfil de seguridad y el perfil FC observados con navitoclax solo o en combinación con ruxolitinib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subjects ≥ 18 years of age - Subjects with documented diagnosis of Intermediate or High-risk Primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis - Subject must be ineligible or unwilling to undergo stem cell transplantation at time of study entry - Subject must have either received prior treatment with ruxolitinib OR another JAK-2 inhibitor therapy OR must not have received any prior treatment with JAK-2 inhibitor. - Subject has palpable splenomegaly. - Subject must meet the laboratory parameters (adequate bone marrow, renal and hepatic function) as defined in the protocol. |
•Pacientes ≥ 18 años de edad •Pacientes con diagnóstico documentado de MF primaria de riesgo intermedio o alto, MF-PPV o MF PTE según lo definido por la clasificación de la Organización Mundial de la Salud •El paciente no debe ser elegible o no debe estar dispuesto a someterse a un trasplante de células progenitoras en el momento de incorporarse al estudio. •El sujeto debe haber recibido tratamiento previo con ruxolitinib u otra terapia inhibidora de JAK-2 O no haber recibido ningún tratamiento previo con inhibidor de JAK-2. •El sujeto tiene esplenomegalia palpable. •El paciente debe cumplir los parámetros de laboratorio (médula ósea, función renal y hepática adecuadas) definidos en el protocolo. |
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E.4 | Principal exclusion criteria |
- Splenic irradiation within 6 months prior to screening, or prior splenectomy. - Leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy). - Subject is currently on medications that interfere with coagulation (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and Low-molecular-weight heparin. - Prior therapy with a BH3 mimetic compound. - Subject has received strong or moderate CYP3A inhibitors within 14 days prior to the administration of the first dose of navitoclax. |
•Irradiación esplénica en los 6 meses previos a la selección o esplenectomía previa •Transformación leucémica (> 10% de blastos en sangre periférica o biopsia de médula ósea) •El paciente recibe actualmente medicamentos que interfieren en la coagulación (incluida warfarina) o la función plaquetaria, a excepción del ácido acetilsalicílico en dosis bajas (hasta 100 mg) y la heparina de bajo peso molecular. •Tratamiento previo con un compuesto mimético BH3 •El paciente ha recibido inhibidores potentes o moderados de la CYP3A en los 14 días previos a la administración de la primera dosis de navitoclax. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percent of subjects who achieve ≥ 35% spleen volume reduction (SVR35) at Week 24 measured by MRI. |
Porcentaje de pacientes que experimenten una disminución ≥ 35% del volumen esplénico (SVR35) en la semana 24, determinada mediante RM. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are percent change in TSS; ORR; anemia response; and change in grade of bone marrow fibrosis. |
Los criterios de valoración secundarios son la variación porcentual de la puntuación total de síntomas, la tasa de respuestas globales, la tasa de respuestas de la anemia, la variación del grado de fibrosis de la médula ósea. |
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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 | No |
E.6.4 | Safety | No |
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 | Yes |
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 |
Tolerability |
Tolerabilidad |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 12 |
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 |
Canada |
United States |
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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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The end-of-study is defined as the date of the last subject's last visit or date of last follow-up contact, whichever is later. |
El final del estudio se define como la fecha de la última visita o del último contacto del último sujeto, lo que sea posterior. |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 6 |