Clinical trial NCT06499025: Treatment of Relapsed or Refractory t(8; 21) AML With Targeted AML1-ETO Neoantigen Cytotoxic T Cells (CTL)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: AML
t(8;21)
Neoantigen
Lead sponsor: BGI, China
Sponsor class: OTHER
Collaborators: name: Shenzhen University General Hospital
First posted: 2024-07-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years old (including 18, 75 years old), gender is not limited;
2. According to WHO (2020) criteria, the subjects are diagnosed for recurrent or refractory t(8:21) acute myeloid leukemia;
3. The subjects voluntarily participate in the study and sign the Informed Consent Form by themselves or their legal guardians;
4. The HLA types of subjects are HLA-A\* 11:01 or HLA-A\*02:01 ;
5. Verified to have AE expression in tumor samples by histopathological examination ;
6. 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 ;
7. No contraindications for collection of mononuclear cells from peripheral blood ;
8. ECOG score ≤1;
9. The survival time is exspected to be≥ 3 months;
10. Have the ability to understand and be willing to sign the informed consent for this test.

Exclusion Criteria:

1. Tumor cells do not express AML1-ETO neoantigen;
2. Active infection;
3. Abnormal liver function \[TBil（total bilirubin)\>1.5×ULN, ALT\>2.5×ULN\], abnormal kidney function \[Scr（serum creatinine)\>1.5×ULN\];
4. Unstable angina or 3/4 class of congestive heart failure according to New York Heart Association, or multiple organ dysfunction;
5. HIV/AIDS patients;
6. Participants who need treatment of long-term anticoagulation (warfarin or heparin) or antiplatelet(aspirin\>300mg/d; Clopidogrel\>75mg/d) ;
7. Participants who received radiotherapy within 4 weeks ,prior to study initiation (blood collection);
8. Known or suspected drug abuse or alcohol dependence;
9. 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;
10. Participants in other clinical trials within 30 days;
11. 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;
12. The investigator evaluates that the subject is unable or unwilling to comply with the requirements of the study protocol;

Primary outcomes:
measure: Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)
timeFrame: 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.
Secondary outcomes:
measure: Complete response rate
timeFrame: Up to 48 weeks
measure: Overall survival (OS)
timeFrame: Up to 72 weeks
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen University General Hospital
state: Guangdong
Study officials:
affiliation: Shenzhen University General Hospital
name: LiXin Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
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