Um estudo de JNJ-88549968 para o tratamento de neoplasias mieloproliferativas mutadas com calreticulina (CALR)
Um primeiro estudo em humanos sobre segurança, farmacocinética e farmacodinâmica de JNJ-88549968, um anticorpo biespecífico de redirecionamento de células T para neoplasias mieloproliferativas com mutação 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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Study Contact
- Número de telefone: 844-434-4210
- E-mail: Participate-In-This-Study1@its.jnj.com
Locais de estudo
-
-
-
Aachen, Alemanha, 52074
- Recrutamento
- Universitaetsklinikum der RWTH Aachen
-
Berlin, Alemanha, 12203
- Recrutamento
- Charite Campus Benjamin Franklin
-
Essen, Alemanha, 45147
- Recrutamento
- Med. Universitatsklinik Essen
-
Hanover, Alemanha, 30625
- Recrutamento
- Medizinische Hochschule Hannover
-
Heidelberg, Alemanha, 69120
- Recrutamento
- Universitaetsklinikum Heidelberg
-
Regensburg, Alemanha, 93053
- Recrutamento
- Universitaetsklinikum Regensburg
-
-
-
-
Alberta
-
Calgary, Alberta, Canadá, T2N 4N1
- Recrutamento
- Arthur J E Child Comprehensive Cancer Centre
-
-
Ontario
-
Toronto, Ontario, Canadá, M5G 1Z5
- Recrutamento
- Princess Margaret Cancer Centre University Health Network
-
-
Quebec
-
Montreal, Quebec, Canadá, H3T 1E2
- Concluído
- Jewish General Hospital
-
-
-
-
-
Beijing, China, 100032
- Recrutamento
- Peking Union Medical College Hospital
-
Hangzhou, China, 310002
- Recrutamento
- The First Affiliated Hospital Zhejiang University School of Medicine
-
Tianjin, China, 301617
- Recrutamento
- Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
-
-
-
-
-
Badalona, Espanha, 08916
- Recrutamento
- Hosp. Univ. Germans Trias I Pujol
-
Valencia, Espanha, 46010
- Recrutamento
- Hosp. Clinico Univ. de Valencia
-
-
-
-
Arizona
-
Goodyear, Arizona, Estados Unidos, 85338
- Recrutamento
- City of Hope Phoenix
-
-
California
-
Duarte, California, Estados Unidos, 91010
- Recrutamento
- City of Hope
-
-
Colorado
-
Aurora, Colorado, Estados Unidos, 80045
- Recrutamento
- UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center
-
-
Florida
-
Tampa, Florida, Estados Unidos, 33612
- Recrutamento
- Moffit Cancer center
-
-
Georgia
-
Atlanta, Georgia, Estados Unidos, 30322
- Recrutamento
- Emory University
-
-
Illinois
-
Zion, Illinois, Estados Unidos, 60099
- Recrutamento
- City of Hope Chicago
-
-
Michigan
-
Ann Arbor, Michigan, Estados Unidos, 48109
- Recrutamento
- University of Michigan
-
Grand Rapids, Michigan, Estados Unidos, 49546
- Recrutamento
- Start Midwest
-
-
New Jersey
-
East Brunswick, New Jersey, Estados Unidos, 08816
- Recrutamento
- START New Jersey
-
New Brunswick, New Jersey, Estados Unidos, 08901
- Recrutamento
- Rutgers Cancer Institute of New Jersey
-
-
New York
-
New York, New York, Estados Unidos, 10065
- Recrutamento
- Memorial Sloan Kettering Cancer Center
-
The Bronx, New York, Estados Unidos, 10467
- Recrutamento
- Montefiore Medical Center
-
-
North Carolina
-
Charlotte, North Carolina, Estados Unidos, 28204
- Recrutamento
- Levine Cancer Institute
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Estados Unidos, 19104
- Recrutamento
- University of Pennsylvania
-
-
South Carolina
-
Greenville, South Carolina, Estados Unidos, 29605
- Recrutamento
- Prisma Health
-
-
Tennessee
-
Nashville, Tennessee, Estados Unidos, 37203
- Recrutamento
- Sarah Cannon Cancer Institute
-
-
Texas
-
Houston, Texas, Estados Unidos, 77030
- Recrutamento
- MD Anderson Cancer Center
-
-
Washington
-
Seattle, Washington, Estados Unidos, 98104
- Recrutamento
- Swedish Cancer Institute
-
-
-
-
-
Paris, França, 75475
- Recrutamento
- Hopital Saint Louis
-
Pierre-Bénite, França, 69495
- Recrutamento
- CH LYON SUD - Hematology
-
Toulouse, França, 31059
- Recrutamento
- Institut Universitaire du Cancer Toulouse Oncopole
-
-
-
-
-
Haifa, Israel, 3436212
- Recrutamento
- Carmel Medical Center
-
Jerusalem, Israel, 9112001
- Recrutamento
- Hadassah University Hospita Ein Kerem
-
Ramat Gan, Israel, 5266202
- Recrutamento
- Sheba Medical Center
-
Tel Aviv, Israel, 64239
- Recrutamento
- Tel Aviv Sourasky Medical Center
-
-
-
-
-
Bologna, Itália, 40138
- Recrutamento
- Policlinico Sant'Orsola Malpighi
-
Milan, Itália, 21022
- Recrutamento
- Policlinico di Milano
-
-
-
-
-
Bunkyō City, Japão, 113 8431
- Recrutamento
- Juntendo University Hospital
-
Kashiwa, Japão, 277 8577
- Recrutamento
- National Cancer Center Hospital East
-
-
-
-
-
London, Reino Unido, SE1 9RT
- Recrutamento
- Guy's and St Thomas' Hospital
-
London, Reino Unido, NW1 2PG
- Recrutamento
- University College London Hospitals Nhs Foundation Trust
-
Oxford, Reino Unido, OX3 7LE
- Recrutamento
- Churchill Hospital
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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:
-
Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
-
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
-
Prior solid organ transplantation
-
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
-
History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
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. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT)
Prazo: Approximately up to 35 days after first dose of study treatment
|
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
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs)
Prazo: Up to 2 years
|
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
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity
Prazo: Up to 2 years
|
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
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968
Prazo: Up to 2 years
|
Serum samples will be analyzed to determine concentrations of JNJ-88549968. |
Up to 2 years
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
Prazo: Up to 2 years
|
Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported. |
Up to 2 years
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate
Prazo: Up to 2 years
|
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
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate
Prazo: Up to 2 years
|
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
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)
Prazo: Up to 2 years
|
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
|
|
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR)
Prazo: Up to 2 years
|
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
|
|
Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
Prazo: Baseline up to 2 years
|
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
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 88549968MPN1001
- 2023-505584-36-00 (Identificador de registro: EUCT number)
- 2023 (Concessão/Contrato do NIH dos EUA)
- 88549968MPN1001 (Outro identificador: Janssen Research & Development, LLC)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano 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
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
produto fabricado e exportado dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .