Um estudo de GDX012 em adultos com leucemia mielóide aguda recidivante ou refratária
Um estudo de fase 1/2a, aberto, escalonamento de dose e expansão de dose para avaliar a segurança e a eficácia de GDX012 em pacientes com leucemia mielóide aguda recidivante ou refratária
GDX012 is a novel cell therapy developed for the treatment of certain types of cancer, including Acute Myeloid Leukemia (AML). The main aims of the study are to learn how safe GDX012 is, how treatment with GDX012 is tolerated and to determine the best dose of GDX012.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
The drug being tested in this study is called GDX012. GDX012 is being tested to evaluate the safety and tolerability in adult participants with AML.
The study will enroll approximately 53 patients in two phases, dose escalation and dose expansion.
During Phase 1 (sequential dose escalation), participants will be assigned to one of the following treatment groups each consisting of 3 to 6 participants to receive GDX012 at one of the three dose levels:
- GDX012 Dose 1
- GDX012 Dose 2
- GDX012 Dose 3
Upon completion of Phase 1, 1 to 2 dose levels will be selected for Phase 2a of the study. At the completion of Phase 2a of the study a single dose may be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D) for future study.
This multi-center trial will be conducted in the United States and Japan. The overall time to participate in the study is approximately 14 months.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos, 35205
- University of Alabama at Birmingham (UAB) Hospital
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California
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Duarte, California, Estados Unidos, 91010
- City of Hope
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Colorado
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Denver, Colorado, Estados Unidos, 80218
- Sarah Cannon/CBCI
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Comprehensive Cancer Center of Northwestern University
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Dana-Farber Cancer Institute
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Missouri
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St Louis, Missouri, Estados Unidos, 63110
- Washington University
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New York
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New York, New York, Estados Unidos, 10065
- Thomas Jefferson University
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- Cleveland Clinic
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Tri-Star BMT/Sarah Cannon Nashville
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Texas
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Houston, Texas, Estados Unidos, 77030
- MD Anderson Cancer Center
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Kashiwa, Japão, 277-8577
- National Cancer Center Hospital East
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion criteria:
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Total body weight of ≥40 kg.
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Must have pathologically confirmed relapsed or refractory acute myeloid leukemia (R/R AML) including:
- Relapsed AML is defined as ≥5% blasts in the bone marrow (BM) or peripheral blood at any time after achieving a CR, CRh, Cri, or MLFS.
- Refractory AML is defined as failure to achieve a CR, CRh, Cri, or MLFS after 1 of the following regimens:
i. Two courses of intensive induction chemotherapy. ii. At least 2 cycles of hypomethylating agent (HMA) or low-dose, cytarabine-based combination regimen.
iii. At least 4 cycles of HMA monotherapy.
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During dose escalation, participants must be ineligible for hematopoietic stem cell transplantation (HSCT).
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Must have an anticipated life expectancy of >3 months before lymphodepletion.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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Participants must have adequate renal, cardiac, hepatic, pulmonary and bone marrow function as defined by the protocol.
Exclusion criteria:
- Diagnosis of acute promyelocytic leukemia.
- Has received or plans to receive any of the excluded therapy/treatment within the specified timeframe before lymphodepleting chemotherapy as defined by the protocol.
- Prior allogeneic HSCT within 3 months of signing informed consent form (ICF) or with ongoing requirement for systemic graft-versus-host therapy.
- Active central nervous system (CNS) involvement.
- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg. cervix, bladder, breast) low grade prostate cancer without treatment requirement unless in remission without treatment for ≥2 years.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Phase 1: Dose Escalation of GDX012 (Dose Level 1)
Participants received GDX012 weight-based dose level 1 as an intravenous (IV) infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 1 was the lowest dose level. |
GDX012 suspension for IV infusion.
Outros nomes:
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care. |
|
Experimental: Phase 1: Dose Escalation of GDX012 (Dose Level 2)
Participants received GDX012 weight-based dose level 2 as an IV infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 2 was higher than Dose Level 1. |
GDX012 suspension for IV infusion.
Outros nomes:
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care. |
|
Experimental: Phase 1: Dose Escalation of GDX012 (Dose Level 3)
Participants received GDX012 weight-based dose level 3 as an IV infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 3 was higher than Dose Level 2. |
GDX012 suspension for IV infusion.
Outros nomes:
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities (DLTs) to Determine the Maximum Tolerated Dose (MTD) of GDX012
Prazo: Up to 30 days post infusion
|
DLTs were defined as events occurring by Day 30 after the first GDX012 infusion considered related to GDX012 if they could not be explained by underlying disease, prior therapy, intercurrent illness, or lymphodepleting chemotherapy. Events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. DLTs included severe non-hematologic toxicities (Grade 3-4, unresolved or involving vital organs), Grade ≥3 graft versus host disease (GvHD) graded per the Mount Sinai Acute GvHD International Consortium recommendations and 2014 National Institutes of Health (NIH) Consensus, Grade 3-4 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) criteria, Grade ≥3 infusion reactions or tumor lysis syndrome (TLS), persistent cytopenia or marrow hypocellularity, and any Grade 5 toxicity attributable to GDX012. |
Up to 30 days post infusion
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Prazo: Up to 14 months
|
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event or a previous condition that has increased in severity or frequency since the administration of study drug. TEAEs are defined as any AE that begins on or after the initiation of treatment with a study intervention or any existing event that worsens following exposure to the study intervention. |
Up to 14 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Percentage of Participants With Disease Response
Prazo: Up to 14 months
|
Percentage of participants with disease response included participants who achieved complete response (CR), complete response with partial hematologic recovery (CRh), or complete response with incomplete hematologic recovery (CRi), based on responses assessed by the investigator according to the 2022 European Leukemia Net [ELN] response criteria for acute myeloid leukemia (AML). CR was defined as the sum of complete remission and complete remission without measurable residual disease (MRD). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. |
Up to 14 months
|
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Percentage of Participants With Measurable Residual Disease (MRD) Negative Status as Determined by Flow Cytometry
Prazo: Up to 14 months
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The MRD negative status was defined as (less than) <0.1% detectable disease based on local assessment of bone marrow and/or blood. |
Up to 14 months
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Duration of Response (DOR)
Prazo: Up to 14 months
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DOR was planned to be assessed for participants with CR, CRh, or CRi and was defined as the time from the date of first documented CR, CRh, or CRi to the date of first documented relapse or death from any cause, whichever comes first. CR was defined as the sum of Complete Remission and Complete Remission without MRD. CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD- . |
Up to 14 months
|
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Event-free Survival (EFS)
Prazo: Up to 14 months
|
EFS was defined as the time from the date of the first GDX012 administration to the date of treatment failure, relapse for those who achieved CR, CRh, or CRi, or death from any cause, whichever came first. CR was defined as the sum of Complete Remission and Complete Remission without MRD (CRMRD-). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. EFS was analyzed using the Kaplan-Meier method. |
Up to 14 months
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Overall Survival (OS)
Prazo: Up to 14 months
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OS was defined as the time from the date of the first GDX012 administration to the date of death from any cause. Participants without documentation of death at the time of analysis were censored at the last contact date. OS was analyzed using the Kaplan-Meier method. |
Up to 14 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Medical Director, Takeda
Publicações e links úteis
Links úteis
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Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
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
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- TAK-012-1501
- jRCT2033240022 (Identificador de registro: jRCT)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Critérios de acesso de compartilhamento IPD
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
- CIF
- CSR
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