CER-1236 in Patients With Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Myelofibrosis (MF)

Официальное название

Phase 1/1b First-in-human Study of Autologous Chimeric Engulfment Receptor T-Cell CER-1236 in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Myelofibrosis (CertainT-1)

Обзор

This is a first in human, multi center, open label, phase 1/1b study to evaluate the safety and preliminary efficacy of CER-1236 in patients with relapsed/refractory (R/R), measurable residual disease (MRD) positive acute myeloid leukemia (AML), or TP53mut disease.

Подробное описание

CER-1236 is a first in class chimeric engulfment receptor T-cell therapy candidate that targets the Tim4 ligand.

This is a first in human, multi center, open label, phase 1/1b study to evaluate the safety and preliminary efficacy of CER-1236 in patients with relapsed/refractory (R/R), measurable residual disease (MRD) positive acute myeloid leukemia (AML), or TP53mut disease.

The study is divided into Part 1 (escalation phase) and Part 2 (expansion phase).

Part 1 (Escalation Phase): The primary objectives of Part 1 are to define the safety of different doses of CER-1236 and to define the recommended dose for Part 2 (RP2D) of CER-1236.

Part 2 (Expansion Phase): The objective of the Part 2 expansion cohort is to evaluate the safety and efficacy of CER-1236 in patients with acute myeloid leukemia.

Вмешательства

• Препарат CER-1236
  an autologous chimeric engulfment receptor T-cell
• Препарат Cyclophosphamide
  Lymphodepleting chemotherapy
• Препарат Fludarabine
  Lymphodepleting chemotherapy
• Препарат Mesna
  Chemoprotectant

Первичные конечные точки

• Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Part 1) [Срок оценки: 2 year]
• Incidence of dose-limiting toxicities (DLTs) of CER-1236 Monotherapy - (Part 1) [Срок оценки: 28 days]
• Estimation of the objective response rate (ORR), complete response (CR), composite complete response (cCR), and measurable residual disease (MRD) negativity rates - (Part 2) [Срок оценки: 2 years]

Вторичные конечные точки (4)

• Estimation of the objective response rate (ORR), complete response (CR), composite complete response (cCR), and measurable residual disease (MRD) negativity rates - (Part 1) [Срок оценки: 2 years]
• PK (Cmax) of CER-1236 - (Part 1) [Срок оценки: 2 years]
• PK (AUC) of CER-1236 - (Part 1) [Срок оценки: 2 year]
• Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Part 2) [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Patients need to have a confirmed diagnosis of de novo or secondary AML, or myelodysplastic syndrome (MDS)/AML with 10% to 19% blasts, per the International Consensus Classification 2022 or the WHO 2022 classification.
• Absolute lymphocyte count >0.3 x 109/L prior to apheresis.
• Eastern cooperative oncology group (ECOG) performance status 0 to 1.

Критерии исключения

• Prior therapy with a permanently integrated, genetically modified cell product.
• No measurable leukemia on the screening bone marrow evaluation prior to any bridging therapy.
• Active autoimmune disease or history of autoimmune disease requiring treatment within the prior 2 years. Patients with history of autoimmune thyroiditis or type 1 diabetes well controlled on replacement regimen are eligible.
• A known hypersensitivity or severe allergy to fludarabine, cyclophosphamide, or study drug components or diluents.
• Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the physician.
• Primary immunodeficiency disorder.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• University of California, Davis Comprehensive Cancer Center — Sacramento
• Colorado Blood Cancer Institute — Denver
• Sarah Cannon Research Insitute — Nashville
• The University of Texas MD Anderson Cancer Center — Houston

Идентификаторы

NCT: NCT06834282 · CER-1-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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