Clinical Study on Safety and Efficacy of Anti-CLL1 /+CD33 CAR T Cells in the Treatment of Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is a single-center, single-arm, open, intravenous drug administration of the safety and efficacy of clinical study.

Detailed Description
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The primary objective of the clinical trial was to evaluate the safety and efficacy of single dose infusion of anti-CLL1 /+CD33 CAR T cells in patients with refractory/recurrent acute myeloid leukemia. A total of about 5 patients with refractory/recurrent acute myeloid leukemia were enrolled in this study, and the target dose range was 1.00 2.50x10^6/kgCAR-positive T cells.

Official Title
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Safety and Efficacy of Anti-CLL1 /+CD33 CAR T Cells in Refractory/Recurrent Acute Myeloid Leukemia: a Single-arm, Non-blind Clinical Study

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: CLL1/+CD33 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient or his/her legal guardian volunteers for the trial and signs an informed consent form; Age range 1-18 years; Acute myeloid leukemia (AML) with CLL1 and CD33 markers (including secondary patients) was diagnosed by pathology, histology and flow cytometry, or complete hematologic remission could not be achieved after 1 course of chemotherapy for hematologic relapse after drug withdrawal ; The main organ functions of the patients were good: (1) liver function: ALT/AST < 3 times the upper limit of normal (ULN) and bilirubin ≤34.2 μmol/l; (2) renal function: creatinine < 220 μmol/l; (3) lung function: oxygen saturation ≥95% ; (4) cardiac function: left ventricular ejection fraction (LVEF)≥40% ; The blood flow of peripheral superficial vein was unobstructed, which could meet the demands of intravenous drip and mononuclear cell collection; ECOG score was 0-2. Exclusion Criteria: The patients had uncontrollable infectious diseases within 4 weeks before the enrollment; Active hepatitis B/C virus; HIV infection, treponema syphilis positive patients; Pathological diagnosis of primary tumors other than acute myeloid leukemia; Suffering from serious autoimmune diseases or immunodeficiency diseases; The patient is allergic to antibodies or cytokines and other macromolecular biological drugs; Pregnant or lactating women; Patients who were considered ineligible for study for other reasons.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 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: CLL1/+CD33 CAR-T<br>The target dose range for subjects was set to be 1.00 2.50x10^6/kg CAR-positive T cells. | Biological: CLL1/+CD33 CAR-T<br>* CLL1/+CD33 CAR T is a type of CAR T cell therapy for patients with treating/relapsed acute myeloid leukemia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cytokine level after CLL1/+CD33 CAR-T infusion | Calculate the change of cytokine level in peripheral blood by flow cytometry after CAR-T infusion. | CAR T cell infusion before and 12 months after infusion | 
| The change characteristics of chimeric antigen receptor(CAR)-T cell number in patients after infusion. | Track CAR-T cells expansion in patients after infusion by flow cytometry | CAR T cell infusion before and 12 months after infusion | 
| The change characteristics of chimeric antigen receptor(CAR)-T cell copy number in patients after infusion. | Track CAR-T cells expansion in patients after infusion by Real-time Quantitative Polymerase Chain Reaction（qPCR） | CAR T cell infusion before and 12 months after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Counting from the beginning of cell transfusion until treatment failure, recurrence, or death (various causes). Subjects without any of these events were counted up to the last follow-up examination date. For patients without CR or CRi, EFS is calculated from the beginning of cell transfusion until disease progression or death. Based on the initial event. | Up to 12 months after CLL1/+CD33 CAR-T infusion | 
| Overall survival | Death from any cause from the beginning of cell transfusion | Up to 12 months after CLL1/+CD33 CAR-T infusion | 
| Duration of Overall Response | The time from the start of cell infusion when CR or PR is first achieved to disease progression. | Up to 12 months after CLL1/+CD33 CAR-T infusion | 
| MRD negative rate | The rate of MRD negative subjects was determined by flow cytometry. | Up to 12 months after CLL1/+CD33 CAR-T infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL1, AML, CD33