| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Newly-diagnosed multiple myeloma (NDMM) patients who are candidates for Autologous Stem Cell Transplant (ASCT). |
| Mieloma múltiple de nuevo diagnóstico (MMND) candidatos a trasplante autólogo de células madre hematopoyéticas (TASPE). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Newly-diagnosed multiple myeloma (NDMM) |
| Mieloma múltiple de nuevo diagnóstico (MMND) |
|
| 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 | 16.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10028229 |
| E.1.2 | Term | Multiple myelomas |
| E.1.2 | System Organ Class | 100000004851 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To compare the efficacy of extended VRD# + ASCT plus ERI& (Arm B) vs. Isatuximab-VRD# + ASCT (Arm A) in terms of proportion of patients who are MRD-negative by next-generation flow cytometry (NGF) after 18 cycles + ASCT*
#VRD: Lenalidomide-Bortezomib-Dex;
&ERI: Early Rescue Intervention with Iberdomide-Isatuximab.
* 18 cycles would be:
- Arms A & C: Induction x4 + ASCT + Consolidation x2 + Continuous x12
- Arm B: Induction x6 + ASCT + Consolidation x2 + Extended x10 |
Comparar la eficacia de VRD extendido + TASPE + IRP (Brazo B) frente a isatuximab-VRD + TASPE (Brazo A) en términos de proporción de pacientes con EMR negativa medida mediante citometría de flujo de nueva generación (NGF) tras 18 ciclos de tratamiento y TASPE (Brazo A: Inducción x4 + TASPE + Consolidación x2 + Continuo x12; Brazo B: Inducción x6 + TASPE + Consolidación x2 + Extendido x10).
- End-point primario B1: Incremento en % pacientes con EMR negativa en brazo A vs. Brazo B (incluyendo VRD extendido solo y considerando todos los que reciban IRP como EMR positiva).
- End-point primario B2: No inferioridad en % pacientes con EMR negativa en brazo A vs. Brazo B (considerando todos los que obtengan EMR negativa tanto con VRD extendido como con IRP). |
|
| E.2.2 | Secondary objectives of the trial |
Safety secondary objective 2.1:
To assess the safety of Isatuximab-VID* + ASCT (Arm C).
*VID: Iberdomide-Bortezomib-Dex.
Note: Due to the experimental nature of the Arm C combination Isatuximab-Iberdomide-Bortezomib-Dex, a safety analysis will be performed with the first 5 patients included in each arm as per section 6.1, a second one when 25 patients in each arm have completed 3 cycles of therapy, and subsequent ones might be required if considered by the DSMC.
Key secondary efficacy objective 2.2:
To explore preliminary efficacy comparison of Arm C (Isatuximab-VID* + ASCT) vs. Arm A (Isatuximab-VRD# + ASCT) in terms of proportion of patients who reach NGF MRD-negative after Induction (4 cycles) + ASCT+ consolidation (two cycles) and 12 continuous treatment cycles.
Key secondary efficacy objective 2.3:
To explore preliminary efficacy comparison of Arm C (Isatuximab- VID*ASCT) vs. Arm B (VRD extended plus ERI) in terms of proportion of patients who reach NGF MRD-negative. |
Objetivos secundarios clave de seguridad
• Determinar la seguridad de isatuximab-VID + TASPE (Brazo C).
Objetivos secundarios clave de eficacia
• Explorar datos preliminares de proporción de pacientes que alcanzan EMR negativa por NGF tras 18 ciclos de tratamiento con isatuximab-VID + TASPE (Brazo C) en comparación con isatuximab-VRD + TASPE (Brazo A).
• Explorar datos preliminares de proporción de pacientes que alcanzan EMR negativa por NGF con isatuximab-VID + TASPE (Brazo C) en comparación con VRD extendido + IRP (Brazo C). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
a.Patient is, in the investigator’s opinion, willing and able to comply with the protocol requirements.
b.Patient must be able to understand the study procedures.
c.Patient has given voluntary written informed consent before performance of any study-related procedure non part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
d.Newly diagnosed multiple myeloma patient who requires start active treatment according to the 2014 IMWG criteria, namely clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcaemia, Anaemia, Renal Insufficiency, or Bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET-CT), and any one or more of the following biomarkers: clonal BMPC% ≥60%, i/u free light ratio ≥100 or > 1 focal lesions on MRI or PET/CT)
e.Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.
f.Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
g.Patient must be ≤ 65 years of age.
i.Female patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
•Is not a woman of childbearing potential (WOCBP)
OR
•Is a WOCBP and
*She understands the potential teratogenic risk to the unborn child
*the need for effective contraception as stated in the protocol, without interruption, 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions and for at least 28 days after the last dose of study treatment.
*She understands and agrees to inform the Investigator if a change or stop of method of contraception is needed.
*She must be capable of complying with effective contraceptive measures.
*She is informed and understands the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.
*She understands the need to commence study treatment as soon as it is dispensed following a negative pregnancy test.
*She understands and accepts the need to undergo pregnancy testing based on the frequency outlined in this plan and in the ICF
*She acknowledges she understands the hazards iberdomide or lenalidomide can cause to an unborn fetus and the necessary precautions associated with the use of iberdomide or lenalidomide.
The Investigator must ensure that a WOCBP:
Complies with the conditions of the pregnancy prevention plan, including confirmation that she has an adequate level of understanding
Acknowledges the aforementioned requirements.
A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
Nonchildbearing potential is defined as follows (by other than medical reasons):
oHas not achieved menarche at some point.
oHas undergone a hysterectomy or bilateral oophorectomy.
oHas been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
j.Male patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Male patient is eligible to participate if he agrees to the following from the time of first dose of study until 6 months after the last dose of iberdomide or lenalidomide to allow for clearance of any altered sperm (Please refer to APPENDIX 11):
•Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a WOCBP
•the need for the use of a condom even if he has had a vasectomy, if engaged in sexual activity with a pregnant female or a FCBP
•the potential teratogenic risk if the subject donates semen or sperm.
•that the effects on fertility are currently unknown, therefore all family planning options and/or alternatives should be thoroughly discussed with the study doctor prior to receiving iberdomide
k.All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia |
● A criterio del investigador, el paciente está dispuesto y capacitado para cumplir los requerimientos del protocolo.
● El paciente debe ser capaz de comprender los procedimientos del estudio.
● El paciente ha firmado voluntariamente el documento de consentimiento informado, comprendiendo además que puede retirar el consentimiento en cualquier momento sin que ello comprometa los cuidados médicos que deba recibir en el futuro.
● MMND que requiera el inicio de un tratamiento activo, de acuerdo con los criterios actualizados del IMWG (Rajkumar SV et al, Lancet Oncol 2014;15:e538-e548).
● Enfermedad secretora medible, definida bien como proteína monoclonal en suero ≥0,5 g/dL o proteína monoclonal en orina ≥200 mg/24 h. En los participantes cuya enfermedad sea medible únicamente mediante cadena ligera libre (CLL) sérica, esta debe ser ≥10 mg/dL, con una ratio sérica de CLL anormal.
● Estadio funcional ECOG ≤2.
● Edad ≤65 años.
Participantes femeninas: deberán adherirse a la normativa local referente al empleo de métodos anticonceptivos en participantes en ensayos clínicos. Una mujer será elegible para el estudio siempre y cuando no se encuentre en período de gestación o de lactancia y cumpla al menos una de las siguientes condiciones:
oNo es una mujer fértil
Ò
oEs una mujer fértil y
-Entiende el potencial riesgo teratogénico para el feto.
-Entiende la necesidad de emplear un método contraceptivo eficaz de forma ininterrumpida desde 28 días antes del inicio del tratamiento, durante toda la duración del tratamiento de estudio, incluyendo interrupciones de dosis, y hasta al menos 28 días después de la última dosis.
-Entiende y acepta informar al investigador se precisa de un cambio o interrupción del método contraceptivo.
-Está capacitada para llevar a cabo las medidas contraceptivas eficaces.
-Comprende las consecuencias derivadas de un embarazo y la necesidad de notificar inmediatamente si hubiera riesgo de gestación.
-Comprende la necesidad de iniciar el tratamiento de estudio tan pronto como esté disponible una vez se disponga de un test de embarazo negativo.
-Comprende y acepta la necesidad de someterse a tests de embarazo con la frecuencia determinada en el plan de trabajo del estudio y en el consentimiento informado.
-Comprende los riesgos los riesgos que lenalidomida e iberdomida puedes suponer para el feto y las necesarias precauciones que esto conlleva.
-Posee un test de embarazo sérico de alta sensibilidad negativo en las 72 horas previas a la primera dosis del tratamiento del estudio.
● Participantes masculinos: el empleo de anticonceptivos debe llevarse a cabo de acuerdo con la normativa local. Se considerarán elegibles si desde la primera dosis de iberdomida hasta 6 meses después de la última están dispuestos a cumplir los siguientes puntos:
o Entiende el potencial riesgo teratogénico en caso de actividad sexual con una mujer fértil.
o Comprende la necesidad de emplear preservativo incluso en caso de vasectomía previa en caso de actividad sexual con una mujer fértil.
o Comprende el potencial riesgo teratogénico en caso de donar semen o esperma.
o Comprende que los efectos sobre la fertilidad de iberdomida se desconocen a días de hoy, por lo que deberá discutir en profundidad con el médico cualquier opción de planificación familiar antes de recibir iberdomida.
• Todas las toxicidades previas relacionadas con el tratamiento (salvo la alopecia) deberán ser ≤Grado 1 (según NCI-CTCAE v5-0) en el momento del reclutamiento. |
|
| E.4 | Principal exclusion criteria |
a.Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.
b.Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma.
c.Prior history of malignancies, other than multiple myeloma (except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or the breast), unless the patient has been free of the disease for ≥ 5 years.
d.Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and/or lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
e.Pregnant or breastfeeding females.
f.Men and women of reproductive potential who are not using effective contraceptive methods
g.Patient is simultaneously enrolled in other interventional clinical trial.
h.Patient has used an investigational drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
i.Patient must not have received prior radiotherapy (except localized palliative radiotherapy for pain, palliation or fracture) within 2 weeks of start of study therapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
j.Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
k.Patient has peripheral neuropathy or neuropathic pain grade 1 with pain or ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
l.Patient evidence of cardiovascular risk including any of the following:
•Myocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function
•Uncontrolled cardiac arrhythmia.
•Screening 12-lead ECG showing a baseline interval QTcF> 470 msec (exception: subjects with pacemaker).
•Patients with uncontrolled hypertension.
m.Patient must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
n.Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria.
o.Evidence of active mucosal or internal bleeding.
p.Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
q.Uncontrolled endocrine diseases
r.Patient with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
s.Patient with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
t.History of interstitial lung disease or ongoing interstitial lung disease.
u.Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment.
v.Patient has an active infection requiring systemic antibiotic, antiviral, or antifungal treatment at the time of starting treatment.
w.Patient has known HIV infection
x.Patient has positive hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study treatment.
y.Patient has positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
z.Patient require concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment)
aa. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to iberdomide or drugs chemically related to iberdomide.
bb. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to isatuximab or drugs chemically related to isatuximab, hypersensitivity reactions, or idiosyncratic reactions to other molecular antibodies.
cc. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to lenalidomide or dexamethasone or drugs chemically related to lenalidomide or dexamethasone. |
● Diagnóstico de amiloidosis primaria, gammapatía monoclonal de significado incierto, mieloma quiescente, leucemia de células plasmáticas o síndrome de POEMS.
● Evidencia clínica de leucostasis en el sistema nervioso central (SNC) o pulmonar, coagulación intravascular diseminada o infiltración del SNC.
● Historia de neoplasias previas (excepto carcinoma cutáneo de células basales o escamosas o carcinoma in situ de cérvix o mama), salvo que el paciente haya estado libre de dicha neoplasia durante ≥5 años.
● Cualquier condición médica grave que suponga un riesgo inaceptable en caso de participar en el estudio; sujetos en tratamiento esteroideo o inmunosupresor crónico.
● Mujeres en período de gestación o de lactancia.
● Hombre o mujeres con potencial reproductor que no empleen métodos anticonceptivos efectivos (métodos de doble barrera, dispositivos intrauterinos, anticonceptivos orales).
● Participación simultánea en otro ensayo clínico.
● Empleo de un fármaco en investigación en los 28 días o las 5 vidas medias (el período que sea más largo) antes de la primera dosis del fármaco en estudio.
● Radioterapia en las 2 semanas previas al inicio del tratamiento del estudio (excepto radioterapia paliativa localizada). Todas las toxicidades relacionadas con la radiación deberán haberse resuelto, no requiriendo corticoides y no asociando neumonitis rádica.
● Cirugía mayor (salvo cifoplastia) en ≤4 semanas previas al inicio del tratamiento.
● Neuropatía periférica o dolor neuropático grado 1 con dolor o grado ≥2 según criterios NCI-CTCAE v5.0.
● Evidencia de riesgo cardiovascular según los siguientes criterios:
o Infarto miocárdico en los 6 meses previos a aleatorización o cualquier condición inestable o no controlada de origen cardiológico.
o Arritmia cardíaca no controlada.
o Intervalo QTcF >470mseg en ECG basal en screening (excepto si marcapasos).
o Hipertensión arterial no controlada.
● Enfermedad biliar o hepática inestable definida como presencia de ascitis, encefalopatía, coagulopatía, hipoalbuminemia, varices gástricas o esofágicas, ictericia persistente o cirrosis (las enfermedades hepáticas crónicas estables como síndrome de Gilbert o colelitiasis asintomática, o afectación hepatobiliar por la neoplasia sí serían aceptables)
● Proceso renal activo (infección, necesidad de diálisis o cualquier condición que comprometa la seguridad del paciente). La proteinuria aislada no es criterio de exclusión.
● Evidencia de sangrado interno o mucoso activo.
● Cualquier condición médica o enfermedad psiquiátrica que dificulte la comprensión del consentimiento informado.
● Enfermedades endocrinas no controladas (por ejemplo, que hayan precisado cambios de medicación en el último mes o ingreso hospitalario en los 3 meses previos).
● Enfermedad pulmonar infiltrativa difusa aguda y/o enfermedad pericárdica aguda.
● Enfermedad pulmonar obstructiva crónica o asma con FEV1<50%.
● Historia previa o activa de enfermedad pulmonar intersticial.
● Enfermedad gastrointestinal que pueda alterar la absorción de tratamientos orales.
● Infección activa que requiera tratamiento sistémico con antibiótico, antiviral o antifúngico.
● Infección VIH conocida.
● Antígeno de superficie de hepatitis B (HBsAg) o anticuerpos anti-core de hepatitis B (HBcAb) positivos en screening o en los 3 meses previos al inicio de tratamiento de estudio.
● Anticuerpos frente a hepatitis C o RNA de hepatitis C positivos en screening o en los 3 meses previos al inicio de tratamiento de estudio. Los pacientes con anticuerpos positivos debido a infección previa resuelta serán elegibles solo si disponen de una determinación de RNA viral negativa. El test de RNA de hepatitis C no es requisito obligado en caso de que la determinación de anticuerpos frente a hepatitis C sea negativa.
● Necesidad de administración de inhibidores o inductores potentes del citocromo P450 (CYP3A4/5) durante el estudio o en los 15 días previos al inicio del tratamiento de estudio.
● Reacción de hipersensibilidad inmediata o diferida, o reacción idiosincrásica a iberdomida o fármacos químicamente relacionados.
● Reacción de hipersensibilidad inmediata o diferida, o reacción idiosincrásica a isatuximab o fármacos químicamente relacionados.
● Reacción de hipersensibilidad inmediata o diferida, o reacción idiosincrásica a lenalidomida o dexametasona o fármacos químicamente relacionados.
● La administración de vacunas vivas o atenuadas está contraindicada en los 30 días previos a la primera dosis y durante el tratamiento. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1.1 Improvement in the percentage of patients MRD-negative in Arm A vs. Arm B when considering B1 endpoint.
B1 endpoint: VRD extended impact only, without considering ERI impact: any patient that require an ERI per protocol before finishing the 18 cycles + ASCT, will be considered MRD-positive at that time, independently of the ERI impact.
1.2 Non-inferiority in the percentage of patients MRD-negative in Arm A vs. Arm B when considering B2 endpoint.
B2 endpoint: VRD extended plus ERI impact: any patient who achieves MRD negativity with ERI before finishing the 18 cycles + ASCT will be considered MRD-negative at that time. |
Comparar la eficacia de VRD extendido + TASPE + IRP (Brazo B) frente a isatuximab-VRD + TASPE (Brazo A) en términos de proporción de pacientes con EMR negativa medida mediante citometría de flujo de nueva generación (NGF) tras 18 ciclos de tratamiento y TASPE (Brazo A: Inducción x4 + TASPE + Consolidación x2 + Continuo x12; Brazo B: Inducción x6 + TASPE + Consolidación x2 + Extendido x10).
- End-point primario B1: Incremento en % pacientes con EMR negativa en brazo A vs. Brazo B (incluyendo VRD extendido solo y considerando todos los que reciban IRP como EMR positiva).
- End-point primario B2: No inferioridad en % pacientes con EMR negativa en brazo A vs. Brazo B (considerando todos los que obtengan EMR negativa tanto con VRD extendido como con IRP). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Whole study |
| todo el estudio |
|
| E.5.2 | Secondary end point(s) |
Safety secondary objective 2.1:
To assess the safety of Isatuximab-VID* + ASCT (Arm C).
*VID: Iberdomide-Bortezomib-Dex.
Note: Due to the experimental nature of the Arm C combination Isatuximab-Iberdomide-Bortezomib-Dex, a safety analysis will be performed with the first 5 patients included in each arm as per section 6.1, a second one when 25 patients in each arm have completed 3 cycles of therapy, and subsequent ones might be required if considered by the DSMC.
Key secondary efficacy objective 2.2:
To explore preliminary efficacy comparison of Arm C (Isatuximab-VID* + ASCT) vs. Arm A (Isatuximab-VRD# + ASCT) in terms of proportion of patients who reach NGF MRD-negative after Induction (4 cycles) + ASCT+ consolidation (two cycles) and 12 continuous treatment cycles.
Key secondary efficacy objective 2.3:
To explore preliminary efficacy comparison of Arm C (Isatuximab- VID*ASCT) vs. Arm B (VRD extended plus ERI) in terms of proportion of patients who reach NGF MRD-negative.
Note: The interim safety and efficacy assessment will be the basis for adapting elements of the trial design and qualifying key secondary efficacy objectives 2.2 and 2.3 as confirmatory.
Other secondary objectives
2.4 Progression-Free Survival (PFS)
2.5 Overall Response Rate (ORR): PR or better (PR, VGPR, CR, sCR).
2.6 Complete Response Rate (CRR): CR or better (CR, sCR).
2.7 Time to Response (TTR), among participants who achieve confirmed PR or better.
2.8 Duration of Response (DoR) among participants who achieved PR or better.
2.9 PFS2
2.10 Overall Survival (OS)
3.1.1 Key Secondary Endpoints
2.2 Improvement in the percentage of patients MRD-negative in Arm C vs. Arm A
2.3 Improvement in the percentage of patients MRD-negative in Arm C vs. Arm B (B2)
For objectives 2.4 to 2.10 the IMWG response criteria or well-established chronological definitions
3.2 Correlative or translational studies
The general objective of the correlative studies is to generate biomarkers and datasets for improving outcomes in MM based on precision medicine and better understanding of tumor and immune cell biology.
Specific objectives of the correlative studies:
3.2.1 Identify genetic risk groups of patients that will benefit the most or that are primary refractory to the treatment schema proposed in the clinical trial.
3.2.2 Evaluate the clinical significance of MRD status using next-generation techniques and define undetectable MRD as the endpoint of the treatment schema proposed.
3.2.3 Understand MRD resistance by using bulk- and single-cell sequencing techniques to compare the genomic signature of matched diagnostic vs. MRD clones isolated by next-generation flow cytometry.
3.3.4 Create an algorithm based on patients’ immune profile and clinical data that enables individualized prediction of outcome based on simultaneous MRD and immune monitoring.
3.3.5 Genetic characterization of tumor cells at diagnosis.
3.3.5 Molecular clonal structure of tumor cells at diagnosis and after therapy.
3.3.6 Molecular characterization of MRD cells persisting to different regimens.
3.3.7 MRD monitoring based on next-generation sequencing (NGS).
3.3.8 MRD monitoring based on next-generation flow (NGF) cytometry.
3.3.9 Next-generation immune monitoring. |
Objetivos secundarios clave de seguridad
• Determinar la seguridad de isatuximab-VID + TASPE (Brazo C).
Objetivos secundarios clave de eficacia
• Explorar datos preliminares de proporción de pacientes que alcanzan EMR negativa por NGF tras 18 ciclos de tratamiento con isatuximab-VID + TASPE (Brazo C) en comparación con isatuximab-VRD + TASPE (Brazo A).
• Explorar datos preliminares de proporción de pacientes que alcanzan EMR negativa por NGF con isatuximab-VID + TASPE (Brazo C) en comparación con VRD extendido + IRP (Brazo C).
Otros objetivos secundarios
• Supervivencia libre de progresión (SLP).
• Tasa de respuesta global (TRG): respuesta parcial (RP) o mejor.
• Tasa de respuesta completa (TRC): respuesta completa (RC) o mejor.
• Tiempo hasta respuesta (THR): en sujetos que alcanzan RP o mejor.
• Duración de la respuesta (DR): en sujetos que alcanzan RP o mejor.
• Supervivencia libre de progresión 2 (SLP2).
• Supervivencia global (SG)
Estudios traslacionales y correlativos
• Identificar grupos de riesgo genético que muestren mayor beneficio o refractariedad primaria al tratamiento propuesto.
• Evaluar el significado clínico de la EMR negativa con técnicas de nueva generación y definir la EMR negativa como variable principal.
• Comprender mejor la resistencia de la EMR, analizando la firma genómica de las células al diagnóstico y de los clones que constituyen la EMR mediante técnicas de secuenciación.
• Establecer un algoritmo basado en los datos clínicos y el perfil inmune que permita establecer predicciones pronósticas individualizadas en base a la evaluación simultánea de EMR y perfil inmunológico.
• Caracterización genética de las células tumorales al diagnóstico y de las células que constituyen la EMR tras cada tratamiento.
• Estructura clonal molecular de las células tumorales al diagnóstico y tras tratamiento.
• Monitorización de EMR basada en secuenciación de nueva generación (NGS) y NGF.
• Monitorización inmunológica de nueva generación. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Whole study |
| Todo el estudio |
|
| 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) | 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 | No |
| E.8.1.3 | Single blind | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 3 |
| 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 | 70 |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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