- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07617285
Allogeneic CAR-T(CT0890B) in NKG2DL+ R/R AML
A Phase I Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Cells (CT0890B) in Patients With NKG2DL-Positive Relapsed/Refractory Acute Myeloid Leukemia
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Xiangyu Zhao, M.D,Ph.D
- Número de teléfono: 010-88325531
- Correo electrónico: Zhao_xy@bjmu.edu.cn
Copia de seguridad de contactos de estudio
- Nombre: Meng Lv, M.D., Ph.D
- Número de teléfono: 010-88316617
- Correo electrónico: drlvmeng@bjmu.edu.cn
Ubicaciones de estudio
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Beijing, Porcelana, 100044
- Reclutamiento
- Peking University People's Hospital
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Sub-Investigador:
- Meng Lv, M.D, Ph.D
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Contacto:
- Meng Lv, M.D,Ph.D
- Número de teléfono: 010-88316617
- Correo electrónico: drlvmeng@bjmu.edu.cn
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Investigador principal:
- Xiangyu Zhao, M.D, Ph.D
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Age 18-70 years (inclusive), male or female.
- Relapsed or refractory acute myeloid leukemia (R/R AML) diagnosed according to the 2022 World Health Organization classification or ELN criteria, with confirmed NKG2D ligand-positive disease.
- Bone marrow blasts ≥5% by morphology.
- Estimated life expectancy >12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Adequate organ function without ongoing supportive care, defined as:
- Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
- Hepatic: ALT and AST ≤2.5 × upper limit of normal (ULN), and total bilirubin ≤2 × ULN;
- Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula);
- Coagulation: activated partial thromboplastin time (APTT) ≤1.5 × ULN and prothrombin time (PT) ≤1.5 × ULN.
c) Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula); d) Coagulation: activated partial thromboplastin time (APTT) ≤1.5 × ULN and prothrombin time (PT) ≤1.5 × ULN.
Exclusion Criteria:
- Participants were diagnosed with acute promyelocytic leukemia (APL), BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase), central nervous system leukemia;
- Participants with a history of epilepsy or other central nervous system disease;
- Participants who have previously received autologous or allogeneic CAR-T therapy;
- Participants who have received autologous stem cell transplantation or allogeneic stem cell transplantation within 12 weeks
- Participants who have received prior immunotherapy targeting NKG2DL;
- Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD;
- Participant has any of the following at screening:
1)Active, uncontrolled systemic infection or requiring intravenous anti-infective agents 2)Any of the following cardiac conditions, including:
- New York Heart Association Class III-IV heart failure;
- History of myocardial infarction, coronary artery bypass grafting, or unstable angina within 6 months prior to Qinglin;
- History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia;
- History of severe nonischemic ardiomyopathy;
- Other cardiac disease that the investigatorbelieve could jeopardize the participant 's well-being or compromise participation in this clinical trial; 3) Active bleeding of clinical significance as judged by the investigator; 4)Requiring supplemental oxygen to maintain oxygen saturation> 92%; 5)Patients with severe chronic obstructive pulmonary disease (COPD) or other lung diseases that cannot tolerate CAR-T treatment as judged by the investigator;
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: CAR-T cells chimeric antigen receptor T cells
CT0890B cells infusion
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Conditioning regimen: Days -9 to -3: Venetoclax administered with a target dose of 200 mg/day. Days -5 to -4: Cytarabine administered at 500 mg/m²/day. Days -5 to -3: Cyclophosphamide at 300 mg/m²/day plus Fludarabine at 30 mg/m²/day. Day 0: Infusion of CT0890B CAR-T cells at one of four dose levels using an i3+3 Dose-Escalation Design: 1.5 × 10⁸ total cells, 3.0 × 10⁸ total cells, 4.5 × 10⁸ total cells, 6.0 × 10⁸ total cells
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Adverse Events (AE) after CT0890B infusion
Periodo de tiempo: 12 months after CT890B infusion
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An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria
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12 months after CT890B infusion
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Dose-limiting toxicity (DLT)
Periodo de tiempo: Up to 28 days after CAR-T cells infusion
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The DLT is evaluated as the proportion of patients who experienced adverse events related to CT0890B that meet the criteria for DLT events after the first infusion
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Up to 28 days after CAR-T cells infusion
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MTD and/or dose range
Periodo de tiempo: Up to 28 days after CAR-T cells infusion
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Evaluate Dose limited toxicity and recommended dosage range after CT0890B infusion
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Up to 28 days after CAR-T cells infusion
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Composite response (CRc)
Periodo de tiempo: 12 months after CT0890B infusion
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The composite response rate (CRc) included complete response (CR), complete response with partial hematologic recovery (CRh), complete response with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS).
Responses were assessed in accordance with the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and the 2022 European LeukemiaNet criteria for acute myeloid leukemia (AML).
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12 months after CT0890B infusion
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Partial response (PR)
Periodo de tiempo: 12 months after CT0890B infusion
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Partial response (PR) was defined and assessed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and the 2022 European LeukemiaNet response criteria for AML.
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12 months after CT0890B infusion
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Rate of Subsequent Stem Cell Transplantation After CAR-T Therapy
Periodo de tiempo: 12 months after CT0890B infusion
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This secondary endpoint was defined as the proportion of patients who proceeded to stem cell transplantation after CAR-T therapy during the study period.
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12 months after CT0890B infusion
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Duration of response (DOR)
Periodo de tiempo: 12 months after CT0890B infusion
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Patients achieving CR, CRi, CRh, or MLFS were included in the duration of response (DOR) analysis set.
DOR was defined as the time from the date of first documented response to the date of disease relapse or death from any cause, whichever occurred first.
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12 months after CT0890B infusion
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Event-free survival (EFS)
Periodo de tiempo: 12 months after CT0890B infusion
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EFS was defined as the time from the date of CAR-T infusion to the earliest occurrence of treatment failure, relapse, or death from any cause. Treatment failure was defined as failure to achieve CR, CRh, CRi, MLFS, or PR at both prespecified efficacy assessments. Relapse included hematologic or extramedullary relapse after achieving CR, CRh, CRi or MLFS. For patients with treatment failure (ineffective therapy), the primary EFS analysis assigned an event time of 1 day (i.e., the time from infusion to treatment receipt). Sensitivity analyses were performed using alternative definitions of event timing, including the actual date of treatment failure, the end of treatment, or the initiation of subsequent anti-leukemia therapy. |
12 months after CT0890B infusion
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Overall survival (OS)
Periodo de tiempo: 12 months after CT0890B infusion
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OS is defined as the time from the date of receiving the infusion to the date of death from any cause.
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12 months after CT0890B infusion
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Minimal Residual Disease (MRD) Negativity Rate
Periodo de tiempo: 12 months after CT0890B infusion
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MRD negativity rate was assessed in participants who achieved CR, CRh, CRi or MLFS.
MRD negativity was defined as <0.01%
abnormal cells among CD45-positive cells as determined by multiparameter flow cytometry (MFC).
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12 months after CT0890B infusion
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Pharmacokinetic Endpoint - Peak expansion (Cmax)
Periodo de tiempo: 12 months after CT0890B infusion
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The maximum concentration or peak value of CT0890B cells in plasma after infusion, measured by CAR copy number.
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12 months after CT0890B infusion
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Time to peak expansion (Tmax) of CT0890B
Periodo de tiempo: 12 months after CT0890B infusion
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The time required to reach the peak expansion (maximum CAR copy number) in plasma following the infusion of CT0890B cells.
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12 months after CT0890B infusion
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Area under the curve (AUC) of CT0890B
Periodo de tiempo: 12 months after CT0890B infusion
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The total cellular exposure in plasma after infusion, calculated based on the area under the CAR copy number-time curve.
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12 months after CT0890B infusion
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In vivo persistence of CT0890B
Periodo de tiempo: Up to 12 months after CT0890B infusion
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The duration for which CT0890B cells remain detectable in the plasma after infusion, monitored via CAR copy number.
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Up to 12 months after CT0890B infusion
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: XiangYu Zhao, M.D, Ph.D, Peking University People's Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
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
Palabras clave
Otros números de identificación del estudio
- CT0890B-CG8001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
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.
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