E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Acute Graft-versus-Host Disease (aGvHD) after allogeneic hematopoietic stem cell transplant |
Prevención de la enfermedad del injerto contra el huésped aguda (EICHa) después del trasplante alogénico de células madre hematopoyéticas |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of Acute Graft-versus-Host Disease (aGvHD) |
Prevención de la enfermedad del injerto contra el huésped aguda (EICHa) |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068908 |
E.1.2 | Term | AGVHD |
E.1.2 | System Organ Class | 100000004870 |
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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 |
The primary objective of the study is to compare the efficacy of defibrotide added to standard of care immunoprophylaxis vs standard of care immunoprophylaxis alone for the prevention of acute graft-versus-host disease (aGvHD) as measured by the cumulative incidence of Grade B-D by Day +100 post-allogeneic hematopoietic stem cell transplant (HSCT) in adult and pediatric patients. |
El objetivo principal del estudio es comparar la eficacia de la adición de defibrotida añadida al tratamiento habitual de inmunoprofilaxis frente al tratamiento habitual de inmunoprofilaxis sólo, para la prevención de la enfermedad del injerto contra el huésped aguda (EICHa) determinada por la incidencia acumulada de EICHa de grado B-D el día +100 después de un alotrasplante de células madre hematopoyéticas (TCMH) en pacientes adultos y pediátricos. |
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E.2.2 | Secondary objectives of the trial |
•To compare the efficacy of defibrotide added to standard of care immunoprophylaxis vs standard of care immunoprophylaxis alone on additional variables: -Grade B-D aGvHD-free survival by Days +100 and +180 post-HSCT -Cumulative incidence of Grade B-D aGvHD by Day +180 post-HSCT -Cumulative incidence of Grade C-D aGvHD by Days +100 and +180 post-HSCT -Cumulative incidence of relapse by Days +100 and +180 post-HSCT •To evaluate steroid use in the treatment of aGvHD by Day +180 post-HSCT •To compare the health-related quality of life (HRQoL) using the following questionnaires: -FACT-BMT-TOI (adults only) -EuroQoL-5D (EQ-5D; version dependent on age group) •To compare the safety of defibrotide added to standard of care immunoprophylaxis vs standard of care immunoprophylaxis alone, including AE profile, SAE profile, laboratory abnormalities, neutrophil and platelet engraftment, graft failure, and infection. |
•Comparar la eficacia de la adición de defibrotida al tratamiento habitual de inmunoprofilaxis con tratamiento habitual de inmunoprofilaxis sólo en variables adicionales: -Supervivencia libre de EICHa de grado B-D los días +100 y +180 post-TCMH -Incidencia acumulada de EICHa de grado B-D el día +180 post-TCMH -Incidencia acumulada de EICHa de grado C-D los días +100 y +180 post-TCMH -Incidencia acumulada de recidivas los días +100 y +180 post-TCMH •Evaluar el uso de esteroides para el tratamiento de la EICHa el día +180 post-TCMH •Comparar la calidad de vida relacionada con la salud con los cuestionarios: -FACT-BMT-TOI (adultos) -EuroQoL-5D (EQ-5D;versión en función del grupo de edad) •Comparar la seguridad de la adición de defibrotida al tratamiento habitual de inmunoprofilaxis con la del tratamiento habitual de inmunoprofilaxis solo;incluyendo el perfil de AA ,perfil de AAG, anomalías de laboratorio, prendimiento de neutrófilos y plaquetas,fracaso del injerto e infección |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must be ≥1 year and <75 years of age at screening and undergoing allogeneic HSCT. 2. Patient must be diagnosed with acute leukemia in morphologic complete remission (CR1 or CR2) or with MDS with no circulating blasts and with less than 5% blasts in the bone marrow 3. Patient must have planned to receive either a myeloablative or reducedintensity conditioning regimen and have an unrelated donor who is HLA matched or single-allele mismatched 4. Graft must be a CD3+ T-cell replete PBSC graft or non-manipulated BM graft. 5. Adult patients must be able to understand and sign a written informed consent. For pediatric patients, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. |
1. El paciente debe tener ≥1 y <75 años de edad en el momento de la selección y estar sometiéndose a un TCMH alogénico. 2. El paciente debe contar con un diagnóstico de leucemia aguda en remisión morfológica completa (RC1 o RC2) o de SMD sin blastocitos circulantes y con menos del 5 % blastocitos en la MO. 3.El paciente debe tener previsto recibir un tratamiento de acondicionamiento mieloablativo o acondicionamiento de baja intensidad y contar con un donante no emparentado con antígenos leucocitarios humanos (HLA) compatibles o con un único alelo discordante. 4. El injerto debe ser un injerto de CMSP con repleción de linfocitos T CD3+ o un injerto de MO sin manipular. 5. Los pacientes adultos deben ser capaces de comprender y firmar un consentimiento informado escrito. En el caso de los pacientes pediátricos, los progenitores/tutores legales o su representante deben ser capaces de comprender y firmar un consentimiento informado escrito. Cuando proceda, se obtendrá el asentimiento conforme a las directrices del centro. |
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E.4 | Principal exclusion criteria |
1. Patient has had a prior autologous or allogeneic HSCT. 2. Patient is using or plans to use an investigational agent for the prevention of GvHD. 3. Patient is receiving or plans to receive other investigational therapy and/ or is enrolled or plans to enroll in a separate clinical study. 4. Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. 5. Patient has a psychiatric illness that would prevent the patient or legal guardian or representative from giving informed consent and/or assent. 6. Patient has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study. 7. Patient is pregnant or lactating and does not agree to stop breastfeeding. 8. Any other condition that would cause a risk to the patient if he/she participated in the trial. 9. Patient has a known history of hypersensitivity to defibrotide or any of the excipients. |
1. El paciente se ha sometido a un TCMH autólogo o alogénico anterior. 2. El paciente está usando o tiene previsto usar un fármaco en investigación para la prevención de la EICH. 3. El paciente está recibiendo o tiene previsto recibir otro tratamiento en investigación o está participando o tiene previsto participar en otro estudio clínico. 4. El paciente, en opinión del investigador, puede que no sea capaz de cumplir los requisitos del estudio relativos a la vigilancia de la seguridad. 5. El paciente padece una enfermedad psiquiátrica que impediría al paciente o a su tutor o representante legal dar su consentimiento o asentimiento informado. 6. El paciente padece una enfermedad grave activa o un trastorno médico concomitante que, en opinión del investigador, interferiría en la realización de este estudio. 7. La paciente está embarazada o en período de lactancia y no está dispuesta a suspender la lactancia. 8. Cualquier otra afección que suponga un riesgo para el paciente si participa en el ensayo. 9. El paciente tiene antecedentes de hipersensibilidad a defibrotida o a alguno de los excipientes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is cumulative incidence of Grade B-D aGvHD by Day +100 post-HSCT. |
El criterio de valoración de seguridad principal es la incidencia acumulada de EICHa de grado B-D el día +100 después de un alotrasplante de células madre hematopoyéticas (TCMH). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day +100 post-HSCT |
Dia +100 post-TCMH |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include the following: • Grade B-D aGvHD-free survival by Days +100 and +180 post-HSCT • Cumulative incidence of Grade B-D aGvHD by Day +180 post-HSCT • Cumulative incidence of Grade C-D aGvHD by Days +100 and +180 post-HSCT • Cumulative incidence of relapse by Days +100 and +180 post-HSCT |
Los criterios de valoración de seguridad secundarios incluyen los siguientes: -Supervivencia libre de EICHa de grado B-D los días +100 y +180 post-TCMH -Incidencia acumulada de EICHa de grado B-D el día +180 post-TCMH -Incidencia acumulada de EICHa de grado C-D los días +100 y +180 post-TCMH -Incidencia acumulada de recidivas los días +100 y +180 post-TCMH |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day +100 and +180 post-HSCT for endpoints except for Cumulative incidence of Grade B-D aGvHD: Day +180 post-HSCT only |
Dia +100 y +180 post-TCMH para los criterios de valoración excepto para Incidencia acumulada de EICHa de grado B-D: Día +180 post-TCMH |
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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 | Yes |
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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Tratamiento habitual |
Standard of Care |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Belgium |
Canada |
France |
Germany |
Italy |
Spain |
Turkey |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |