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

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: AML; t(8;21); Neoantigen
• Intervention / Treatment: Biological: targeted AML1-ETO neoantigen cytotoxic T cells (CTL); Drug: Cyclophosphamide injection; Drug: Decitabine Injection; Drug: Liposome mitoxantrone

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Shenzhen university General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 or demonstrated persistant AML1-ETO positiving or genetic MRD recurrence after ≥3 cycles of intensive chemotherapy, as confirmed by quantitative PCR;
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. Possessing the AML1-ETO(RUNX1-RUNX1T1) funsion gene;
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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: targeted AML1-ETO neoantigen cytotoxic T cells (CTL); The escalating doses of cells (CTL) in this study will be 5*10^7 cells and 1*10^8 cells.

Biological: 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.; Drug: Cyclophosphamide injection; Cyclophosphamide injection will be performed in -10 to -8d before neoantigen cytotoxic T cells transfusion; Drug: Decitabine Injection; Decitabine Injection will be performed in -12 to -8d before neoantigen cytotoxic T cells transfusion; Drug: Liposome mitoxantrone; Liposome mitoxantrone will be performed in -9 to -8d before neoantigen cytotoxic T cells transfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)	To determine the incidence of AE and SAE in clinical trials	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	The total number of subjects with complete response (CR) confirmed and the proportion of subjects in the corresponding analysis set	Up to 48 weeks
Overall survival (OS)	The time from cell transfusion to death who have completed the prescribed dose. If the sujects is lost to follow-up, the last known date of surival wil be OS deletion time	Up to 72 weeks

Collaborators and Investigators

• Sponsor: BGI, China
• Collaborators: Shenzhen University General Hospital
• Investigators: Principal Investigator: LiXin Wang, Doctor, Shenzhen university General Hospital

Publications and helpful links

General Publications

• Godugu K, Rajabi M, Mousa SA. RETRACTED: Godugu et al. Anti-Cancer Activities of Thyrointegrin alphavbeta3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780. Cancers (Basel). 2024 May 15;16(10):1880. doi: 10.3390/cancers16101880.
• Biernacki MA, Foster KA, Woodward KB, Coon ME, Cummings C, Cunningham TM, Dossa RG, Brault M, Stokke J, Olsen TM, Gardner K, Estey E, Meshinchi S, Rongvaux A, Bleakley M. CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia. J Clin Invest. 2020 Oct 1;130(10):5127-5141. doi: 10.1172/JCI137723.
• Blankenstein T, Leisegang M, Uckert W, Schreiber H. Targeting cancer-specific mutations by T cell receptor gene therapy. Curr Opin Immunol. 2015 Apr;33:112-9. doi: 10.1016/j.coi.2015.02.005. Epub 2015 Feb 27.
• Sahin U, Tureci O. Personalized vaccines for cancer immunotherapy. Science. 2018 Mar 23;359(6382):1355-1360. doi: 10.1126/science.aar7112.
• van der Lee DI, Reijmers RM, Honders MW, Hagedoorn RS, de Jong RC, Kester MG, van der Steen DM, de Ru AH, Kweekel C, Bijen HM, Jedema I, Veelken H, van Veelen PA, Heemskerk MH, Falkenburg JHF, Griffioen M. Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia. J Clin Invest. 2019 Feb 1;129(2):774-785. doi: 10.1172/JCI97482. Epub 2019 Jan 14.
• Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci PG, Martelli MF; GIMEMA Acute Leukemia Working Party. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005 Jan 20;352(3):254-66. doi: 10.1056/NEJMoa041974.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 7, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 22, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine; Cyclophosphamide
• Other Study ID Numbers: BGI-007; KYLLHS-20230402A (Other Identifier: Ethics Committee of Shenzhen University General Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No