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

NCT06499025 | Enrolling By Invitation Early Phase 1 DMC

• 2 other identifiers: BGI-007KYLLHS-20230402A
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 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.

Conditions

AML; t(8;21); Neoantigen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Complete response rate

  Up to 48 weeks

• Overall survival (OS)

  Up to 72 weeks

Study Arms (1)

targeted AML1-ETO neoantigen cytotoxic T cells (CTL)

EXPERIMENTAL

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); Drug: Cyclophosphamide injection; Drug: Decitabine Injection; Drug: Liposome mitoxantrone

Interventions

targeted AML1-ETO neoantigen cytotoxic T cells (CTL) BIOLOGICAL

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.

targeted AML1-ETO neoantigen cytotoxic T cells (CTL)

Cyclophosphamide injection DRUG

Cyclophosphamide injection will be performed in -10 to -8d before neoantigen cytotoxic T cells transfusion

targeted AML1-ETO neoantigen cytotoxic T cells (CTL)

Decitabine Injection DRUG

Decitabine Injection will be performed in -12 to -8d before neoantigen cytotoxic T cells transfusion

targeted AML1-ETO neoantigen cytotoxic T cells (CTL)

Liposome mitoxantrone DRUG

Liposome mitoxantrone will be performed in -9 to -8d before neoantigen cytotoxic T cells transfusion

targeted AML1-ETO neoantigen cytotoxic T cells (CTL)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• BGI, China: lead
• Shenzhen University General Hospital: collaborator

Study Sites (1)

Shenzhen University General Hospital

Shenzhen, Guangdong, China

Location

Related Publications (6)

• 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.

  PMID: 38792024 BACKGROUND

• 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.

  PMID: 15659725 BACKGROUND

• 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.

  PMID: 32831296 BACKGROUND

• 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.

  PMID: 25728991 BACKGROUND

• Sahin U, Tureci O. Personalized vaccines for cancer immunotherapy. Science. 2018 Mar 23;359(6382):1355-1360. doi: 10.1126/science.aar7112.

  PMID: 29567706 BACKGROUND

• 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.

  PMID: 30640174 BACKGROUND

MeSH Terms

Interventions

Cyclophosphamide; Decitabine

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• LiXin Wang, Doctor

  Shenzhen University General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2024
• First Posted: July 12, 2024
• Study Start: February 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)