E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Defined by parent protocol. The study will enroll all adult and paediatric subjects who received at least one genetically modified T cells infusion in a previous Celgene sponsored study (see protocol section 4.2).
Initially it is planned to enroll patients from parent studies BB2121-MM-001 (EudraCT 2017-002245-29; for adult patients with relapsed and refractory multiple myeloma) and JCAR017-BCM-001 (EudraCT 2017-000106-38; for adult subjects with aggressive B-Cell Non-Hodgkin Lymphoma). |
Definido en el protocolo principal. Se incluirá a todos los sujetos adultos y pediátricos que hayan recibido al menos una infusión de linfocitos T modificados genéticamente en un estudio anterior de Celgene (sección 4.2 protocolo). Está previsto incluir pacientes del estudio BB2121-MM-001 (EudraCT 2017-002245-29; pacientes adultos con mieloma múltiple recidivante y resistente al tratamiento) y JCAR017-BCM-001 (EudraCT 2017-000106-38; pacientes adultos con linfoma no Hodgkin de células B agresivo |
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E.1.1.1 | Medical condition in easily understood language |
Defined by parent protocol |
Definido en el protocol principal |
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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 | LLT |
E.1.2 | Classification code | 10025631 |
E.1.2 | Term | Malignant lymphoid neoplasm NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 assess the risk of delayed adverse events (AEs) following exposure to gene-modified (GM) T cells - To monitor for long-term persistence of GM T cells, including analysis of vector integration sites, as appropriate. - To monitor for generation of replication competent retroviruses (RCR) - To assess long-term efficacy following treatment with GM T cells - Describe growth, developmental outcome, and sexual maturity status for subjects who were aged < 18 years at time of GM T cell treatment - To assess long term health-related quality of life following treatment with GM T cells |
- Evaluar el riesgo de acontecimientos adversos (AA) tardíos tras la exposición a linfocitos T modificados genéticamente (MG). • Supervisar la persistencia a largo plazo de los linfocitos T GM, incluido el análisis de los puntos de integración de los vectores, según proceda. • Supervisar la generación de retrovirus con capacidad de replicación (RCR). • Evaluar la eficacia a largo plazo tras el tratamiento con linfocitos T MG. • Describir el crecimiento, el desarrollo y la madurez sexual de los pacientes < 18 años en el momento del tratamiento con linfocitos T MG. • Evaluar la calidad de vida relacionada con la salud a largo plazo tras el tratamiento con linfocitos T MG. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. All adult and pediatric subjects who received at least one gene-modified (GM) T cell infusion in a previous Celgene sponsored or Celgene alliance partner sponsored study, and have discontinued, or completed the post-treatment follow-up period in the parent treatment protocol, as applicable. 2. Subject (and, parental/legal representative, when applicable) must understand and voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. |
1. Todos los sujetos adultos y pediátricos que hayan recibido al menos una infusión de linfocitos T modificados genéticamente (MG) en un estudio anterior patrocinado por Celgene o por un socio de Celgene y que hayan interrumpido o finalizado el periodo de seguimiento posterior al tratamiento en el protocolo de tratamiento principal, como corresponda. 2. El sujeto (y su padre/madre/representante legal, cuando proceda) deben entender y firmar voluntariamente un DCI/DAI antes de que se realice ninguna evaluación o procedimiento relacionados con el estudio. 3. El sujeto debe poder y estar dispuesto a cumplir el calendario de visitas del estudio y otros requisitos del protocolo. |
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E.4 | Principal exclusion criteria |
Not Applicable. |
No applicable. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: - Incidence of delayed Adverse Events suspected to be related to prior gene-modified (GM) T cell therapy, including: - New malignancies (hematologic or solid) - New neurologic disorder, or exacerbation of a pre-existing neurologic disorder - New rheumatologic or autoimmune disorder, or exacerbation of a prior rheumatologic or other autoimmune disorder - New hematologic disorder - Other new clinical conditions considered related to the prior GM T cell therapy by the investigator. Hospitalizations, regardless of relationship to prior treatment, including reasons and dates
- Persistence of GM T cells - Analysis of vector integration sites - Incidence of replication-competent retroviruses (RCR) - Height, weight, growth, and organ development will be assessed for all pediatric subjects - Sexual maturity status for pediatric subjects
Efficacy Where applicable: - Tumor Response Status - Date of Disease Progression - Date of Relapse - Survival Status
HRQoL Measurement of health-related quality of life (HRQoL) changes as assessed using instruments administered in the parent treatment protocol |
Seguridad: - Incidencia de acontecimientos adversos tardíos que se sospeche que están relacionados con el tratamiento con linfocitos T modificados genéticamente (MG) anterior, tales como: - Nuevas neoplasias malignas (hemáticas o sólidas). - Un nuevo trastorno neurológico o empeoramiento de uno preexistente. - Un nuevo trastorno reumatológico o autoinmunitario, o empeoramiento de uno preexistente. - Un nuevo trastorno hemático. - Otros cuadros clínicos que, en opinión del investigador, estén relacionados con el tratamiento con linfocitos T MG anterior. - Hospitalizaciones, con independencia de su relación con el tratamiento anterior, incluidos los motivos y las fechas.
- Persistencia de los linfocitos T MG. - Análisis de los puntos de integración del vector. - Incidencia de retrovirus con capacidad de replicación (RCR). - Se evaluarán la altura, peso, crecimiento y desarrollo de los órganos de todos los sujetos pediátricos. - Madurez sexual de los pacientes pediátricos.
Eficacia Cuando corresponda: - Estado de la respuesta del tumor. - Fecha de la progresión de la enfermedad. - Fecha de la recidiva. - Estado de supervivencia.
CVRS Determinación de los cambios en la calidad de vida relacionada con la salud (CVRS), evaluada mediante los instrumentos administrados en el protocolo de tratamiento principal. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
HRQoL: Up to 5 years from last GM T cells infusion Other endpoints: Up to 15 years from last GM T cells infusion |
CVRS: hasta 5 años después de la última infusión de linfocitos T MG. Otros puntos finales: hasta 15 años después de la última infusión de linfocitos T MG |
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E.5.2 | Secondary end point(s) |
Not Applicable. |
No applicable. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not Applicable. |
No applicable. |
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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 | 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 |
Health-related quality of life (HRQoL) |
Calidad de vida relacionada con la salud (CVRS) |
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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) | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Protocolo de seguimiento a largo plazo |
Long-Term Follow-up Protocol |
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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 | 0 |
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 | 3 |
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 |
Austria |
Belgium |
Canada |
Finland |
France |
Germany |
Italy |
Japan |
Netherlands |
Spain |
Switzerland |
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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The End of Trial is defined as either the date of the last visit of the last subject or the date of receipt of the last data point from the last subject that is required for primary analysis, as pre-specified in the protocol, whichever is the later date. |
El final del ensayo se define bien como la fecha de la última visita del último sujeto, o bien como la fecha de recepción del último punto de datos del último sujeto que se necesita para el análisis principal, con arreglo a lo especificado previamente en el protocolo, lo que ocurra más tarde. |
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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 | 15 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 15 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |