Clinical Trials Register

Summary
EudraCT Number:	2019-001413-16
Sponsor's Protocol Code Number:	68284528MMY3002
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-12-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2019-001413-16

A.3

Full title of the trial

A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against BCMA, versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects with Relapsed and Lenalidomide-Refractory Multiple Myeloma

Estudio aleatorizado en fase III que compara JNJ-68284528, una terapia de linfocitos T con receptor quimérico para el antígeno (T-CAR) dirigida contra el antígeno de maduración de los linfocitos B (BCMA), frente a pomalidomida, bortezomib y dexametasona (PVd) o daratumumab, pomalidomida y dexametasona (DPd) en sujetos con mieloma múltiple en recidiva y refractario a lenalidomida.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Randomized Study Comparing JNJ-68284528 versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects with Relapsed and Lenalidomide-Refractory Multiple Myeloma

Estudio aleatorizado en fase III que compara JNJ-68284528 frente a pomalidomida, bortezomib y dexametasona (PVd) o daratumumab, pomalidomida y dexametasona (DPd) en sujetos con mieloma múltiple en recidiva y refractario a lenalidomida.

A.3.2

Name or abbreviated title of the trial where available

CARTITUDE-4

A.4.1

Sponsor's protocol code number

68284528MMY3002

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Research & Development, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31 71 524 21 66
B.5.5	Fax number	+31 71 524 21 10
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	JNJ-68284528
D.3.2	Product code	JNJ-68284528
D.3.4	Pharmaceutical form	Dispersion for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	JNJ-68284528
D.3.9.3	Other descriptive name	JNJ-68284528
D.3.9.4	EV Substance Code	SUB197280
D.3.10	Strength
D.3.10.1	Concentration unit	kg kilogram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.5 to 1.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Yes
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Yes
D.3.11.3.5.1	CAT classification and reference number	The EMA/CAT considers that product JNJ-68284528, falls within the definition of gene therapy medicinal product. Product ref.: H0005095
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Yes
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1153
D.3 Description of the IMP
D.3.1	Product name	Daratumumab
D.3.2	Product code	JNJ-54767414
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DARATUMUMAB
D.3.9.1	CAS number	945721-28-8
D.3.9.2	Current sponsor code	JNJ-54767414
D.3.9.3	Other descriptive name	HuMax-CD38, 3003-005
D.3.9.4	EV Substance Code	SUB175772
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	VELCADE
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	bortezomib
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BORTEZOMIB
D.3.9.1	CAS number	179324-69-7
D.3.9.4	EV Substance Code	SUB20020
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	IMNOVID
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/672
D.3 Description of the IMP
D.3.1	Product name	IMNOVID
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pomalidomide
D.3.9.1	CAS number	19171-19-8
D.3.9.3	Other descriptive name	POMALIDOMIDE
D.3.9.4	EV Substance Code	SUB33379
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dexamethasone
D.2.1.1.2	Name of the Marketing Authorisation holder	mibe GmbH Arzneimittel Munchener Str. 15
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dexamethasone
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXAMETHASONE
D.3.9.3	Other descriptive name	Dexamethson
D.3.9.4	EV Substance Code	SUB07017MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsed and lenalidomide-refractory multiple myeloma (MM)

Mieloma múltiple en recidiva y refractario a lenalidomida

E.1.1.1

Medical condition in easily understood language

Multiple Myeloma

Mieloma múltiple

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10028228
E.1.2	Term	Multiple myeloma
E.1.2	System Organ Class	100000004864

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 the efficacy of JNJ 68284528 with standard therapy, either PVd or DPd

Comparar la eficacia de JNJ‑68284528 con el tratamiento de referencia, ya sea PVd o DPd

E.2.2

Secondary objectives of the trial

1.To further compare the efficacy of JNJ 68284528 with standard therapy, either PVd or DPd
2. To assess the safety profile of JNJ 68284528
3. To characterize the pharmacokinetics and pharmacodynamics of JNJ-68284528
4. To assess the immunogenicity of JNJ 68284528
5. To evaluate the impact of JNJ-68284528 treatment on the health-related quality of life of subjects compared with standard therapy, either PVd or DPd

1.Comparar la eficacia de JNJ 68284528 con el tratamiento de referencia, PVd o DPd
2.Evaluar el perfil de seguridad de JNJ 68284528
3.Caracterizar la farmacocinética y la farmacodinamia de JNJ-68284528
4.Evaluar la inmunogenicidad de JNJ-68284528
5.Evaluar la repercusión del tratamiento con JNJ-68284528 en la calidad de vida relacionada con la salud de los sujetos en comparación con el tratamiento de referencia, PVd o DPd

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be at least 18 years of age.
2. Have documented diagnosis of MM as defined by the criteria below:
-Multiple myeloma diagnosis according to the IMWG diagnostic criteria
-Measurable disease at screening as defined by any of the following:
-Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
-Light chain MM without measurable M-protein in the serum or the urine: Serum free light chain ≥10 mg/dL and abnormal serum free light chain ratio.
3. Have received 1 to 3 prior lines of therapy including a PI and IMiD. Subject must have undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was the best response to the line of therapy
4. Have documented evidence of PD by IMWG criteria based on investigator’s determination on or within 6 months of their last regimen.
5. Subjects with only 1 prior line of therapy must have progressed within 36 months of a stem cell transplant or if not transplanted, then within 42 months of starting initial therapy.
6. Be refractory to lenalidomide per IMWG consensus guidelines (progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For subjects with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy.
7. Have an ECOG Performance Status score of 0 or 1
8. Have clinical laboratory values as specified in the protocol.

For additional information see section 5.1 of the protocol

1. Tener al menos 18 años.
2. Tener un diagnóstico confirmado de MM según criterios:
· Diagnóstico de MM según los criterios de diagnóstico del IMWG.
· Una enfermedad medible en la selección definida por:
· Concentración de la proteína M ≥1,0 g/dl o concentración de proteína M en orina ≥200 mg/24 horas, o
· MM de cadenas ligeras sin proteína M medible en suero u orina: Cadena ligera libre en suero ≥10 mg/dl y proporción anormal de cadenas ligeras libres en suero.
3.Haber recibido de 1 a 3 líneas de tratamiento, incluyendo un IP y un IMiD. El sujeto debe haber recibido al menos 1 ciclo de tratamiento completo por cada línea de tratamiento, salvo que la EP fuera la mejor respuesta a la línea de tratamiento.
4.Tener evidencia de EP según criterios del IMWG o en un plazo de 6 meses desde su últim tratamiento.
5.Los sujetos con solo 1 línea de tratamiento previa deben haber progresado en los 3 años posteriores al TACM o, si no se han sometido a un trasplante, en los 3 años posteriores al inicio del tratamiento.
6.Ser refractario a la lenalidomida conforme a IMWG (progresión a los 60 días o antes de que transcurran 60 días desde la finalización del tratamiento). La progresión en el mantenimiento de lenalidomida cumplirá este criterio. Para los sujetos con más de 1 línea de tratamiento previa, no es necesario ser refractario a la lenalidomida en la línea de tratamiento anterior más reciente.
7. ECOG de 0 o 1.
8.Tener valores clínicos de laboratorio que cumplan los siguientes criterios durante la fase de selección (de acuerdo con protocolo).

Para más información consultar sección 5.1 del protocolo.

E.4

Principal exclusion criteria

1.Prior treatment with CAR-T therapy directed at any target.
2. Any previous therapy that is targeted to BCMA.
3. Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia.
4. Subjects with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive PVd as standard therapy or bridging therapy; however, subject may receive DPd as standard therapy or bridging therapy.
5. Was vaccinated with live attenuated vaccines within 4 weeks prior to randomization
6. Subject received any antitumor therapy as specified in the protocol, prior to randomization
7. Active malignancies (ie, progressing or requiring treatment change in the last
24 months) other than the disease being treated under study. Refer to the protocol for allowed exceptions.
8. Plasma cell leukemia at the time of screening, Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL amyloidosis.
9. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to JNJ 68284528 or its excipients, including dimethylsulfoxide, or to fludarabine, cyclophosphamide, tocilizumab, pomalidomide, dexamethasone.
10. Stroke or seizure within 6 months of signing ICF.
11. Received either of the following:
-An allogenic stem cell transplant within 6 months before apheresis. Subjects who received an allogeneic transplant must have stopped all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. Subjects with active graft-versus-host disease are excluded.
-An autologous stem cell transplantation ≤ 12 weeks before apheresis.
12. Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM.
For additional information, see section 5.2 of the protocol

1. Tratamiento anterior con cualquier terapia dirigida de linfocitos T-CAR.
2. Cualquier terapia previa dirigida a los antígenos de maduración de células B (BCMA).
3. Toxicidad continua de un tratamiento previo contra el cáncer que no se ha resuelto volviendo a los niveles iniciales o hasta un grado 1 o inferior, salvo en caso de alopecia.
4. Los sujetos con neuropatía periférica de grado 1 con dolor o neuropatía periférica de grado 2 o superior no podrán recibir PVd como tratamiento de referencia o terapia puente; sin embargo, el sujeto puede recibir DPd como tratamiento de referencia o terapia puente.
5. Haber sido vacunado en las 4 semanas anteriores a la aleatorización.
6. El sujeto recibió cualquier terapia antitumoral (ver protocolo), antes de la aleatorización.
7. Presencia de enfermedades malignas (que hayan requerido tratamiento en los últimos 24 meses). Consultar protocolo para ver excepciones.
8. Leucemia de células plasmáticas en la selección, macroglobulinemia de Waldenström, síndrome POEMS (polineuropatía, organomegalia, endocrinopatía, proteína monoclonal y alteraciones cutáneas) o amiloidosis AL primaria.
9. Contraindicaciones o alergias potencialmente mortales, hipersensibilidad o intolerancia a JNJ 68284528 o sus excipientes, incluido dimetilsulfóxido o fludarabina, ciclofosfamida, tocilizumab, pomalidomida, dexametasona.
10. Accidente cerebrovascular o convulsiones en los 6 meses previos a la firma del consentimiento.
11. Haber recibido cualquiera de los siguientes:
• Un alotrasplante de células madre en los 6 meses anteriores a la aféresis. Durante 6 semanas se deben haber suspendido los medicamentos inmunodepresores a los sujetos que hayan recibido un alotrasplante sin indicios de enfermedad de injerto contra huésped. Se excluyen los sujetos con enfermedad de injerto contra huésped.
• Un alotrasplante de células madre ≥12 semanas antes de la aféresis.
12. Antecedentes o afectación activa conocida del sistema nervioso central (SNC) o signos clínicos de afectación meníngea del MM.

Para más información consultar sección 5.2 del protocolo.

E.5 End points

E.5.1

Primary end point(s)

PFS

Supervivencia libre de progresión

E.5.1.1

Timepoint(s) of evaluation of this end point

Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 6 years)

Evaluación mensual desde la aleatorización hasta la enfermedad progresiva (EP) o muerte, lo que ocurra antes (aprox. 6 años)

E.5.2

Secondary end point(s)

1. Rate of CR/sCR
2. Overall MRD negative rate
3. Rate of MRD negativity in subjects with CR/sCR at
12 months ±3 months
4. Rate of sustained MRD negative status
5. OS
6. ORR
7. PFS on next line of therapy (PFS2)
8. Incidence and severity of adverse events
9. Pharmacokinetic and pharmacodynamic markers
including but not limited, to systemic cytokine
concentrations, and markers of CAR-T cells, T cell
expansion (proliferation), and persistence via
monitoring CAR-T positive cell counts and CAR
transgene level.
10. Presence of anti-JNJ-68284528 antibodies
11. Change from baseline in health-related quality of life
(HRQoL) subscale scores from the European
Organization for Research and Treatment of Cancer
(EORTC) QLQ-C30, Multiple Myeloma Symptom and
Impact Questionnaire (MySIm-Q), EuroQol Five
Dimension Questionnaire (EQ-5D-5L), Patient Global
Impression of Severity (PGIS), and the Patient Reported Outcomes version of the Common
Terminology Criteria for Adverse Events (PRO-CTCAE)
items.

1. Tasa de RC/RCe
2. Tasa global de la EMR negativa.
3. Tasa de EMR negativa en sujetos con RC/RCe a los 12 meses ±3 meses.
4. Tasa de la EMR negativa mantenida.
5. SG
6. TRG
7. SLP en la siguiente línea de terapia (SLP2)
8. Incidencia y gravedad de los eventos adversos.
9. Marcadores farmacodinámicos y farmacocinéticos, entre los que se incluyen concentraciones generales de citocinas y marcadores de linfocitos T-CAR, expansión de linfocitos T (proliferación) y supervivencia mediante la supervisión del recuento de linfocitos T-CAR positivos y el nivel del transgén CAR.
10. Presencia de anti cuerpos anti-JNJ-68284528.
11. Cambio respecto al momento de referencia en las puntuaciones de la subescala de la calidad de vida relacionada con la salud (CdVRS) mediante el cuestionario QLQ-C30 de la Organización Europea para la Investigación y Tratamiento del Cáncer (EORTC), el cuestionario Síntomas e impacto del mieloma múltiple (MySIm-Q), el cuestionario EuroQol de cinco dimensiones (EQ-5D-5L), la impresión global de la gravedad del paciente (PGIS) y la versión de los resultados comunicados por el paciente (PRO) de los Criterios de terminología común para acontecimientos adversos (PRO-CTCAE).

E.5.2.1

Timepoint(s) of evaluation of this end point

Followed until the end of the study (approximately up to 6 years)

Seguimiento hasta fin de estudio (aprox. hasta 6 años)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

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

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Belgium

Denmark

France

Germany

Israel

Italy

Japan

Netherlands

Spain

Sweden

United Kingdom

United States

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

The end of study is when approximately 250 deaths have occurred in the study.

se considerará fin de estudio cuando hayan ocurrido 250 muertes

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

320

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

236

F.4.2.2

In the whole clinical trial

400

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the end of the study, the sponsor will continue to monitor subjects treated with JNJ-68284528 for up to 15 years after administration of JNJ-68284528 on a separate long-term follow-up study for complications of lentiviral integration, potential delayed adverse events, including SPMs.

Después de completar este estudio, el promotor hará un seguimiento de los sujetos que hayan sido tratados con JNJ-68284528 hasta 15 años después de la última dosis con JNJ-68284528 en un estudio de seguimiento para evaluar posibles complicaciones de integración de lentivirus, y potenciales acontecimientos adversos incluyendo nuevas enfermedades malignas.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-01-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-16

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials