Clinical Study of CD38 CAR-T Cells in the Treatment of Hematological Malignancies

Study Overview
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Brief Summary
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Clinical Study on the Safety and Effectiveness of CD38 CAR-T Cells in the Treatment of CD38-positive Hematological Malignancies

Detailed Description
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The CAR-T cell injection uses immune cells from healthy donors, and is the final product obtained after CAR genetic modification, cell expansion, culture, screening, preparation, sub-packaging, and release inspection. CD38 is highly expressed in myeloid leukemia, and it has been confirmed that the treatment of targeting CD38 has great potential in the treatment of CD38-positive hematological malignancies. The center intends to apply for a clinical trial of CD38 CAR-T cells to treat CD38-positive hematological malignancies on the basis of preliminary research.

Official Title
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Clinical Study on the Safety and Effectiveness of CD38 CAR-T Cells in the Treatment of CD38-positive Hematological Malignancies

Conditions
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AML

Intervention / Treatment
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* Biological: CD38 CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients is histologically diagnosed with CD38-positive AML according to the NCCN Clinical Practice Guidelines in Oncology：Acute Myeloid Leukemia（Version 2.2021）; 2. The diagnosis is consistent with r/r CD38 + AML, and includes any of the following conditions: No CR was obtained after 2 courses of standard chemotherapy The first induction was CR, but the duration of CR was less than 12 months No CR was obtained after the first or multiple remedial treatment Relapse twice or more 3. The number of blast cells in bone marrow was more than 5% (morphology) and / or > 1% (flow cytometry); 4. No active lung infection, inhaled air oxygen saturation ≥92%; 5. The estimated survival time is more than 3 months; 6. ECOG score was 0-2; 7. The patients or their legal guardians voluntarily participated in the trial and signed the informed consent. Exclusion Criteria: 1. Patients with history of epilepsy or other central nervous system diseases; 2. Patients with prolonged QT or severe heart disease; 3. Pregnant or lactating women (the safety of this therapy for unborn children is unknown); 4. The patients with uncontrolled active infection; 5. Active hepatitis B or hepatitis C virus infection; 6. Previous application of gene therapy; 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; 8. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl; 9. Those who suffer from other uncontrolled diseases are not suitable to join the study; 10. HIV infection; 11. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
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: Treatment of CD38-positive Hematological Malignancies<br>Administration of CD38 CAR T-cells A dose levels of 2-8*10E6/kg are administrated for each subject. | Biological: CD38 CAR T-cells<br>* Drug: CD38 CAR T-cells Each subject receive CD38 CAR T-cells by intravenous infusion Other Name: CD38 CAR T-cells injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD38 CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 90 days after CD38 CAR T-cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CAR-T cells | In peripheral blood and bone marrow | From admission to the end of the follow-up, up to 2 years | 
| Disease control rate, DCR | The percentage of patients with remission and stable disease after treatment in the total evaluable cases. | From Day 28 CD38 CAR-T infusion up to 2 years | 
| Duration of remission, DOR | The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause | 24 months post CD38 CAR-T cells infusion | 
| Progression-free survival, PFS | The time from cell reinfusion to the first assessment of disease progression or death from any cause | 24 months post CD38 CAR-Tcells infusion | 
| Overall survival, OS | The time from the cell reinfusion to death due to any cause | From CD38 CAR-T infusion to death，up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, CD38 CAR T-cell therapy