E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Multiple Myeloma |
Mieloma múltiple en recaída o refractario |
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E.1.1.1 | Medical condition in easily understood language |
Bone marrow Cancer |
Cáncer de células plasmáticas |
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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 | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000054086 |
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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 compare carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in patients with multiple myeloma who have relapsed after 1 to 3 prior therapies. |
Comparar carfilzomib, dexametasona y daratumumab (KdD) con carfilzomib y dexametasona (Kd) en términos de supervivencia libre de progresión (SLP) en pacientes con mieloma múltiple en recaída después de 1 a 3 terapias previas. |
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E.2.2 | Secondary objectives of the trial |
*To compare the Overall Response Rate (ORR; defined as the proportion of best overall response of stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]) between arms *To compare the rate of minimal residual disease negative-complete response (MRD[-]CR) in bone marrow aspirates at 12 months (+/-4 weeks) as determined by next generation sequencing (NGS) between arms *To compare the Overall Survival (OS) between arms |
- Comparar la Tasa de respuesta global (TRG) (definida como la proporción de mejor respuesta global de la respuesta completa estricta [RCe], la respuesta completa [RC], la respuesta parcial muy buena [RPMB] y la respuesta parcial [RP]) entre brazos - Comparar la Tasa de respuesta completa de enfermedad residual mínima negativa (RCERM[-]) en aspiraciones de médula ósea a los 12 meses (± 4 semanas) determinada mediante secuenciación de nueva generación (NGS) entre brazos - Comparar la Supervivencia global (SG) entre brazos |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male or female subjects ≥ 18 years of age • relapsed or progressive multiple myeloma after last treatment • received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy • prior therapy with carfilzomib is allowed as long as the patient had at least a PR to most recent therapy with carfilzomib, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and will have at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not proteasome inhibitors or CD38 antibodies during this 6-month carfilzomib treatment free interval) • prior therapy with anti-CD38 antibodies is allowed as long as the patient had at least a PR to most recent therapy with CD38 antibody, was not removed due to toxicity, did not relapse within 60 days from intensive treatment (at least every other week) of CD38 antibody therapy, and will have at least a 6-month CD38 antibody treatment-free interval from last dose received until first study treatment. |
• Hombre o mujer ≥ 18 años de edad. • Mieloma múltiple en recaída o progresivo después del último tratamiento. • Haber recibido entre 1 y 3 líneas de tratamiento anteriores para el mieloma múltiple (el tratamiento de inducción seguido de trasplante de células progenitoras y el tratamiento de consolidación/mantenimiento se considerará como 1 línea de tratamiento; consulte el apéndice E para obtener instrucciones). • El tratamiento previo con carfilzomib está autorizado siempre que el paciente experimentara como mínimo una RP al tratamiento más reciente con carfilzomib, no fuera retirado debido a toxicidad, no sufriera una recaída durante los 60 días posteriores a la interrupción del tratamiento con carfilzomib y tenga un intervalo de como mínimo 6 meses sin tratamiento con carfilzomib desde la última dosis recibida hasta el primer tratamiento del estudio. (Los pacientes pueden recibir tratamiento de mantenimiento con fármacos que no sean inhibidores del proteosoma o anticuerpos anti-CD38 durante este intervalo de 6 meses sin tratamiento con carfilzomib). • El tratamiento previo con anticuerpos anti-CD38 está autorizado siempre que el paciente experimentara como mínimo una RP al tratamiento más reciente con anticuerpos anti-CD38, no fuera retirado debido a toxicidad, no sufriera una recaída durante los 60 días posteriores al tratamiento intensivo (al menos cada dos semanas) con anticuerpos anti-CD38 y tenga un intervalo de como mínimo 6 meses sin tratamiento con anticuerpos anti-CD38 desde la última dosis recibida hasta el primer tratamiento del estudio. |
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E.4 | Principal exclusion criteria |
• prior participation in a Janssen daratumumab phase 3 study • known moderate or severe persistent asthma within the past 2 years • known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of predicted normal • active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization |
• Haber participado previamente en un estudio de fase 3 de daratumumab de Janssen. • Asma moderada o grave persistente conocida en los últimos 2 años. • Enfermedad pulmonar obstructiva crónica (EPOC) conocida con un VEF1 < 50% del nivel normal previsto. • Insuficiencia cardíaca congestiva activa (de clase III a IV, según la New York Heart Association [NYHA]), isquemia sintomática, arritmias no controladas, anomalías clínicamente significativas en el electrocardiograma (ECG), ECG de selección con un intervalo QT corregido (QTc) > 470 ms, enfermedad del pericardio o infarto de miocardio durante los 4 meses previos a la aleatorización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PFS defined as time from randomization until disease progression or death from any cause. Response and disease progression determined by a blinded Independent Review Committee (IRC). |
SLP definida como el tiempo desde la aleatorización hasta la progresión de la enfermedad o la muerte por cualquier causa. La respuesta y la progresión de la enfermedad serán determinadas por un comité de revisión independiente (CRI) enmascarado. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS: Every 28 days throughout the study |
SLP: cada 28 dias a lo largo el estudio |
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E.5.2 | Secondary end point(s) |
*ORR: defined as the proportion of best overall response of sCR, CR, VGPR, and PR by IRC *MRD[-]CR rate, MRD[-]CR defined as achievement of complete response by IRC per IMWG-URC and MRD[-] status as assessed by NGS (at a 10-5 level, pending clinical validation) at 12 months. * OS |
• TRG: definida como la proporción de mejor respuesta global de la respuesta completa estricta (RCe), la respuesta completa (RC), la respuesta parcial muy buena (RPMB) y la respuesta parcial (RP), determinadas por el CRI. • Tasa de RCERM[-]: la RCERM[-] se define como la consecución de una RC, determinada por el CRI, según los criterios de respuesta uniforme del Grupo de Trabajo Internacional del Mieloma (IMWG-URC) y el estado de ERM[-] evaluado mediante NGS (a un nivel de 10-5, pendiente de validación analítica) a los 12 meses. • SG. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ORR: Every 28 days throughout the study MRD[-]CR: 12 months from starting the study OS: Throughout the study and every 3 months during longterm follow-up |
- TRG: cada 28 dias a lo largo del estudio - Tasa de RCERM[-]: 12 meses desde el inicio del estudio - SG: a lo largo del estudio y cada 3 meses durante el seguimiento a largo plazo |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
France |
Greece |
Hungary |
Japan |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Spain |
Taiwan |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 primary completion date is the date when the last subject is assessed for the final collection of data for the primary endpoint(s), for the purposes of conducting the primary analysis. The end of study date is defined as the date when the last subject is assessed in the study (ie, last subject last visit), following any additional parts in the study (eg, long-term follow-up), as applicable. This is anticipated to occur at approximately ~58 months from first subject enrolled. |
La fecha de finalización principal es aquella en que el último sujeto es evaluado para recopilar los últimos datos de la variable(s) principal(es) con el fin de llevar a cabo el análisis principal. El fin del estudio se define como la ultima visita de evaluación del sujeto (p.ej: ultima visita vultimo sujeto),después de cualquier parte adicional en el estudio (p.ej seguimiento a largo plazo)según aplique. Esto está previsto que ocurra aprox. 58 meses después de incluir al primer sujeto. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |