Un estudio de JNJ-88549968 para el tratamiento de neoplasias mieloproliferativas mutadas en calreticulina (CALR)
Un primer estudio en humanos sobre la seguridad, farmacocinética y farmacodinamia de JNJ-88549968, un anticuerpo biespecífico redireccionador de células T para neoplasias mieloproliferativas con mutación CALR
The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Study Contact
- Número de teléfono: 844-434-4210
- Correo electrónico: Participate-In-This-Study1@its.jnj.com
Ubicaciones de estudio
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Aachen, Alemania, 52074
- Reclutamiento
- Universitaetsklinikum der RWTH Aachen
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Berlin, Alemania, 12203
- Reclutamiento
- Charite Campus Benjamin Franklin
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Essen, Alemania, 45147
- Reclutamiento
- Med. Universitatsklinik Essen
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Hanover, Alemania, 30625
- Reclutamiento
- Medizinische Hochschule Hannover
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Heidelberg, Alemania, 69120
- Reclutamiento
- Universitaetsklinikum Heidelberg
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Regensburg, Alemania, 93053
- Reclutamiento
- Universitaetsklinikum Regensburg
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Alberta
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Calgary, Alberta, Canadá, T2N 4N1
- Reclutamiento
- Arthur J E Child Comprehensive Cancer Centre
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Ontario
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Toronto, Ontario, Canadá, M5G 1Z5
- Reclutamiento
- Princess Margaret Cancer Centre University Health Network
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Quebec
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Montreal, Quebec, Canadá, H3T 1E2
- Terminado
- Jewish General Hospital
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Badalona, España, 08916
- Reclutamiento
- Hosp. Univ. Germans Trias I Pujol
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Valencia, España, 46010
- Reclutamiento
- Hosp. Clinico Univ. de Valencia
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Arizona
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Goodyear, Arizona, Estados Unidos, 85338
- Reclutamiento
- City of Hope Phoenix
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California
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Duarte, California, Estados Unidos, 91010
- Reclutamiento
- City of Hope
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Reclutamiento
- UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center
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Florida
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Tampa, Florida, Estados Unidos, 33612
- Reclutamiento
- Moffit Cancer center
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Reclutamiento
- Emory University
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Illinois
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Zion, Illinois, Estados Unidos, 60099
- Reclutamiento
- City of Hope Chicago
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- Reclutamiento
- University of Michigan
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Grand Rapids, Michigan, Estados Unidos, 49546
- Reclutamiento
- Start Midwest
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New Jersey
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East Brunswick, New Jersey, Estados Unidos, 08816
- Reclutamiento
- START New Jersey
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New Brunswick, New Jersey, Estados Unidos, 08901
- Reclutamiento
- Rutgers Cancer Institute of New Jersey
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New York
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New York, New York, Estados Unidos, 10065
- Reclutamiento
- Memorial Sloan Kettering Cancer Center
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The Bronx, New York, Estados Unidos, 10467
- Reclutamiento
- Montefiore Medical Center
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North Carolina
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Charlotte, North Carolina, Estados Unidos, 28204
- Reclutamiento
- Levine Cancer Institute
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Reclutamiento
- University of Pennsylvania
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South Carolina
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Greenville, South Carolina, Estados Unidos, 29605
- Reclutamiento
- Prisma Health
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Reclutamiento
- Sarah Cannon Cancer Institute
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Texas
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Houston, Texas, Estados Unidos, 77030
- Reclutamiento
- MD Anderson Cancer Center
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Washington
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Seattle, Washington, Estados Unidos, 98104
- Reclutamiento
- Swedish Cancer Institute
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Paris, Francia, 75475
- Reclutamiento
- Hopital Saint Louis
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Pierre-Bénite, Francia, 69495
- Reclutamiento
- CH LYON SUD - Hematology
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Toulouse, Francia, 31059
- Reclutamiento
- Institut Universitaire du Cancer Toulouse Oncopole
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Haifa, Israel, 3436212
- Reclutamiento
- Carmel Medical Center
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Jerusalem, Israel, 9112001
- Reclutamiento
- Hadassah University Hospita Ein Kerem
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Ramat Gan, Israel, 5266202
- Reclutamiento
- Sheba Medical Center
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Tel Aviv, Israel, 64239
- Reclutamiento
- Tel Aviv Sourasky Medical Center
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Bologna, Italia, 40138
- Reclutamiento
- Policlinico Sant'Orsola Malpighi
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Milan, Italia, 21022
- Reclutamiento
- Policlinico di Milano
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Bunkyō City, Japón, 113 8431
- Reclutamiento
- Juntendo University Hospital
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Kashiwa, Japón, 277 8577
- Reclutamiento
- National Cancer Center Hospital East
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Beijing, Porcelana, 100032
- Reclutamiento
- Peking Union Medical College Hospital
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Hangzhou, Porcelana, 310002
- Reclutamiento
- The First Affiliated Hospital Zhejiang University School of Medicine
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Tianjin, Porcelana, 301617
- Reclutamiento
- Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
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London, Reino Unido, SE1 9RT
- Reclutamiento
- Guy's and St Thomas' Hospital
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London, Reino Unido, NW1 2PG
- Reclutamiento
- University College London Hospitals Nhs Foundation Trust
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Oxford, Reino Unido, OX3 7LE
- Reclutamiento
- Churchill Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Be greater than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
- Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
- Participants with ET and MF with risk characteristics as described in the protocol
- Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (<=) 2
- For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
Exclusion Criteria:
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Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
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Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (>=) 3 years after treatment ended are allowed to enter the study
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Prior solid organ transplantation
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Either of the following regarding hematopoietic stem cell transplantation:
- Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or
- Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
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History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)
In dose escalation (Part 1), participants will receive JNJ-88549968. For myelofibrosis (MF) participants only, the study will explore a Phase 1b cohort in which the janus kinase (JAK) inhibitor ruxolitinib or momelotinib is started in combination with JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule (s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. Additional Cohorts may be added to assess different formulation or delivery methods. In dose expansion (Part 2, Part 2b [US only]), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1, Part 1b [US only]). |
JNJ-88549968 will be administered. For US sites: Ruxolitinib will be administered for participants with MF only. For US sites: Momelotinib will be administered for participants with MF only. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT)
Periodo de tiempo: Approximately up to 35 days after first dose of study treatment
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Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. For US only: A DLT is any adverse event attributed to study treatment that meets the criteria for severity and duration and that occurs during the evaluation periods unless it can be incontrovertibly attributed to disease or other extraneous cause such as an accident. |
Approximately up to 35 days after first dose of study treatment
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs)
Periodo de tiempo: Up to 2 years
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An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity
Periodo de tiempo: Up to 2 years
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An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events [ICANS]) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. |
Up to 2 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968
Periodo de tiempo: Up to 2 years
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Serum samples will be analyzed to determine concentrations of JNJ-88549968. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
Periodo de tiempo: Up to 2 years
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Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate
Periodo de tiempo: Up to 2 years
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ORR is defined as the percentage of participants who achieve partial response (PR) and complete response (CR) according to modified International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) criteria and modified European Leukemia Net (ELN) consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate
Periodo de tiempo: Up to 2 years
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CR rate is defined as the percentage of participants who achieve a best response of CR according to disease as defined in modified IWG-MRT criteria and modified ELN consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)
Periodo de tiempo: Up to 2 years
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TTR is defined for participants who achieved PR or CR as the time from the first dose of study treatment to first response of PR or CR according to modified IWG-MRT criteria and modified ELN consensus report. |
Up to 2 years
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Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR)
Periodo de tiempo: Up to 2 years
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DOR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression, as defined in modified IWG-MRT criteria and modified ELN consensus report, or death, whichever comes first. |
Up to 2 years
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Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
Periodo de tiempo: Baseline up to 2 years
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Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO) questionnaire will be reported in this outcome measure. |
Baseline up to 2 years
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 88549968MPN1001
- 2023-505584-36-00 (Identificador de registro: EUCT number)
- 2023 (Subvención/contrato del NIH de EE. UU.)
- 88549968MPN1001 (Otro identificador: Janssen Research & Development, LLC)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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