Treatment of Relapsed or Refractory t(8; 21) AML With Targeted AML1-ETO Neoantigen Cytotoxic T Cells (CTL)

Официальное название

A Clinical Study to Evaluate the Safety and Initial Efficacy of Targeted AML1-ETO Neoantigen Cytotoxic T Cells (CTL) in the Treatment of Relapsed or Refractory t(8; 21) AML

Обзор

1. To evaluate the safety and tolerability of targeted AML1-ETO neoantigen cytotoxic T cells (CTL) in the treatment of relapsed or refractory acute myeloid leukemia . 2. To evaluate the effectiveness of targeted AML1-ETO neoantigen cytotoxic T cells (CTL)，by the complete response rate(CRR) and overall survival (OS) followed.

Подробное описание

This is a single arm、open label and non-randomied clinical trial ，divided into dose exploration phase (Part A) and dose extension phase (Part B).

Part A: Plan to enroll six subjects to evaluate the safety and tolerabilty of targeted neoantigen cytotoxic T cells (CTL),determine dose-limiting toxicity(DLT),explore the maximum tolerated dose (MTD) or the recommended dose for later clilnical studies.The DLT observation period is 28 days after the infusion of targeted neoantigen cytotoxic T cells (CTL) iniection. One dose group(total number of cells is 5×10\^7/bag) and the another one (total number of cells is 10×10\^7 /bag )is setted by the 3+3 test design.

Part B: Ten subjects are planned to be enrolled in the dose-exploration phase with the recommended dose, to further evaluate the safety、tolerability and its efficacy of targeted neoantigen cytotoxic T cells (CTL) in relapsed or refractory acute myeloid leukemia.

Вмешательства

• Биопрепарат targeted AML1-ETO neoantigen cytotoxic T cells (CTL)
  After subject screening, peripheral blood mononuclear cell #PBMC# donors matching half or more of the subject's HLA matching will undergo blood collection to prepare neoantigen cytotoxic T cells. Neoantigen cytotoxic T cells preparation is expected to be 25-30 days after blood collection. In this study, the bridging therapy will be allowed before Chemotherapy preconditioning. Chemotherapy preconditioning will be performed before neoantigen cytotoxic T cells transfusion.
• Препарат Cyclophosphamide injection
  Cyclophosphamide injection will be performed in -10 to -8d before neoantigen cytotoxic T cells transfusion
• Препарат Decitabine Injection
  Decitabine Injection will be performed in -12 to -8d before neoantigen cytotoxic T cells transfusion
• Препарат Liposome mitoxantrone
  Liposome mitoxantrone will be performed in -9 to -8d before neoantigen cytotoxic T cells transfusion

Первичные конечные точки

• Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0) [Срок оценки: From preconditioning or cell reinfusion to one year after cell reinfusion or the initiation of other antitumor therapy or the discontinuation of the trial for other reasons, whichever occurred first.]

Вторичные конечные точки (2)

• Complete response rate [Срок оценки: Up to 48 weeks]
• Overall survival (OS) [Срок оценки: Up to 72 weeks]

Критерии участия

Критерии включения

• Age 18-75 years old (including 18, 75 years old), gender is not limited;
• According to WHO (2020) criteria, the subjects are diagnosed for recurrent or refractory t(8:21) acute myeloid leukemia or demonstrated persistant AML1-ETO positiving or genetic MRD recurrence after ≥3 cycles of intensive chemotherapy, as confirmed by quantitative PCR;
• The subjects voluntarily participate in the study and sign the Informed Consent Form by themselves or their legal guardians;
• The HLA types of subjects are HLA-A\* 11:01 or HLA-A\*02:01;
• Possessing the AML1-ETO(RUNX1-RUNX1T1) funsion gene;
• Disease progression after adequate first-line systemic treatment for remission, or disease progression after first-line or above systemic systemic treatment for ≥2 cycles , or without remission (CR or PR) after≥4 cycles of treatment ;
• No contraindications for collection of mononuclear cells from peripheral blood ;
• ECOG score ≤1;
• The survival time is exspected to be≥ 3 months;
• Have the ability to understand and be willing to sign the informed consent for this test.

Критерии исключения

• Tumor cells do not express AML1-ETO neoantigen;
• Active infection;
• Abnormal liver function \[TBil（total bilirubin)>1.5×ULN, ALT>2.5×ULN\], abnormal kidney function \[Scr（serum creatinine)>1.5×ULN\];
• Unstable angina or 3/4 class of congestive heart failure according to New York Heart Association, or multiple organ dysfunction;
• HIV/AIDS patients;
• Participants who need treatment of long-term anticoagulation (warfarin or heparin) or antiplatelet(aspirin>300mg/d; Clopidogrel>75mg/d) ;
• Participants who received radiotherapy within 4 weeks ,prior to study initiation (blood collection);
• Known or suspected drug abuse or alcohol dependence;
• Patients with mental disorders or other medical conditions are unable to obtain informed consent and cooperate to complete the requirements of experimental treatment and examination procedures;
• Participants in other clinical trials within 30 days;
• Pregnant or lactating women and male subjects (or their partners) or female subjects who plan to become pregnant during the study period and within 6 months after the end of the study ,and do not wish to use a medically approved effective contraceptive method (such as an IUD or condom) during the study period;
• The investigator evaluates that the subject is unable or unwilling to comply with the requirements of the study protocol;

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shenzhen University General Hospital — Шэньчжэнь

Публикации

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Идентификаторы

NCT: NCT06499025 · BGI-007 · KYLLHS-20230402A

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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