Clinical Study of Universal CAR-γδT Cell Injection in the Treatment of Patients With Relapsed AML After Transplantation

Study Overview
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Brief Summary
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This is an open single-arm clinical study aimed at evaluating the efficacy and safety of universal γδT cell injection in the treatment of patients with relapsed AML after transplantation

Detailed Description
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Main purpose: To evaluate the safety and effectiveness of universal CAR-γδT cell injection in the treatment of patients with relapsed AML after transplantation Secondary purpose: to investigate the in vivo dynamics characteristics of universal CAR-γδT cells after infusion and explore reasonable therapeutic doses through climbing tests in different dose groups.

Official Title
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Clinical Study of Universal CAR-γδT Cell Injection in the Treatment of Patients With Relapsed AML After Transplantation

Conditions
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AML

Intervention / Treatment
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* Biological: CAR-γδT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinically diagnosed recurrence of AML after receiving transplant therapy; Flow cytometry (FCM) or immunohistochemical detection of tumor cells confirmed CD123 positive; Age ≥2 years old and <65 years old; Survival is expected to be greater than 3 months from the date of signing of the informed consent; KPS 80 points or more; The functions of vital organs shall meet the following conditions: 1) EF>50%, and no obvious ECG abnormality; 2) SpO2 90% or more; 3) Cr 2.5 ULN or less; 4) ALT And AST≤5ULN, TBil≤3ULN; 7. Subjects who plan to become pregnant must agree before study enrollment and after study duration of 6 months Use contraception; Inform the investigator immediately if the subject is pregnant or suspected to be pregnant; 8. Subject or guardian understands and signs the informed consent; Exclusion Criteria: 1. Other diseases that have not been effectively controlled, including but not limited to persistent or poorly controlled infections and diseases Congestive heart failure, unstable angina pectoris, arrhythmias, poorly controlled lung disease Or mental illness; 2. Other active malignant tumors; 3. Complicated with severe infection that cannot be effectively controlled; 4. Active hepatitis B (HBVDNA) or HCV RNA [HCVRNA] test was positive); 5. Human immunodeficiency virus (HIV) infection or syphilis infection; 6. Have a history of severe allergy to biological products (including antibiotics); 7. Acute graft-versus-host reaction (GVHD) was still present one month after discontinuation of immunosuppressant therapy Allogeneic hematopoietic stem cell transplantation patients; 8. Female subjects are in pregnancy and lactation; 9. Active autoimmune diseases requiring systemic immunosuppression; 10. Conditions that the investigator believes may increase the risk of the subject or interfere with the results of the test;

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR--γδT<br>Patients will be treated with CAR--γδT cells | Biological: CAR-γδT<br>* Biological: CAR-γδT; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;<br>* Other names: CD19 CAR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within first one month after CAR-γδT infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity | First 1 month post CAR-T cells infusion | 
| Efficacy: Remission Rate | Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、No remission(NR) | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of response (DOR) | duration of response (DOR) | 24 months post CAR-T cells infusion | 
| Efficacy: progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of CAR- γδT cells in the genomes of PBMC by qPCR method | 3 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method | First 1 month post CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML γδT CAR-