Clinical Study of Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Myeloid Leukemia

Study Overview
=================
Brief Summary
-----------------
Researchers plan to enroll a total of 100 patients with relapsed, refractory acute myeloid leukemia (AML) to receive a single dose of autologous CAR T cells.The safety of CAR T therapy was evaluated by observing adverse events after cell therapy;The efficacy of CAR-T therapy was evaluated against the outcome of patients' own past standard treatment regimens or historical data.Blood and bone marrow were collected before and 12 months after infusion to detect the number and activity of CAR T cells, and to evaluate the pharmacokinetics (PK) of CAR T cells.

Official Title
-----------------
Clinical Study of Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Myeloid Leukemia

Conditions
-----------------
Acute Myeloid Leukemia

Intervention / Treatment
-----------------
* Drug: Anti-CLL1 CART cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The diagnosis of myeloid leukemia was clear;Refractory treatment was defined as: (1) 2 patients who did not achieve partial remission after treatment with standard induced remission regimens.② The patients who relapsed within 6 months after the first remission were also called early recurrence.③ The failure relapsed 6 months after the initial response, but was retreated with the original induced response regimen.(4) multiple relapse.Relapse is defined as: patients who achieve complete remission after treatment, more than 5% of leukemia cells in the bone marrow, also known as intramedullary recurrence;Or the presence of leukaemia outside the bone marrow, also known as extramedullary relapse (usually in the central nervous system, testicular leukemia is the most common); Diseased cells were confirmed to express CD123, CLL1 and other targets; KPS > 60 points; Expected survival of more than 3 months; No gender limitation, age 2-75; Patients clinically diagnosed as high-risk type, refractory type of recurrence or not eligible for standard treatment; No serious mental disorders; Sufficient heart, liver and renal function (a. Liver function: ALT/AST < 3 times upper limit of normal value (ULN) and bilirubin ≤34.2μmol/L;B. Renal function: creatinine < 220μmol/L;C. Lung function: indoor oxygen saturation ≥95%;D. Cardiac function: left ventricular ejection fraction (LVEF) ≥40%;); No other serious diseases (such as autoimmune diseases, immune deficiency, organ transplantation) that are in conflict with this program; Can cooperate with trial management and follow-up; Patients voluntarily participated in the study and signed the informed consent Exclusion Criteria: History of other malignant tumors; Uncontrolled active infection; Patients with underlying diseases requiring systemic use of glucocorticoids; Acute or chronic GVHD; T-cell inhibitor therapy; Pregnant and lactating women; Patients with active hepatitis B; Other conditions considered by the investigator to be inappropriate for the study (HIV infection, intravenous drug addiction, etc.), or other conditions that may affect the analysis of the results of the clinical study.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>CLL-1 targeting CAR-T treatment | Drug: Anti-CLL1 CART cells<br>* In this study, patients with acute myeloid leukemia were treated with autologous anti-CLL1 CAR T cells by a single, intravenous infusion.Blood and bone marrow were collected before and 12 months after infusion to detect the number and activity of CAR T cells, and to evaluate the efficacy of CAR T cells.<br>* Other names: CLL1 CAR-T;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AE after CAR-T infusion | Incidence of adverse events after CAR-T infusion Data. The records of adverse events (AE) should include: description of AE and all related symptoms, occurrence time, severity, duration, measures taken, final results and outcomes. According to NCI CTC AE 5.0 standard, AE was scored Grade. Safety evaluation indexes include but are not limited to the following contents Any spontaneously reported and all directly observed adverse events; Any abnormal changes in vital signs and physical examination; The abnormal results of laboratory examination, physical examination and blood examination with clinical significance after treatment | up to 12 months after CAR-T infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR rate | Overall response rate (ORR=CR+CRi) after CAR-T infusion | 1month, 2 months, 3months, 6months ,12months after CAR-T infusion | 
| PFS | Progression free survival (PFS) after CAR-T infusion | 1month, 2 months, 3months, 6months ,12months after CAR-T infusion | 
| OS | overall survival (OS) after CAR-T infusion | 1month, 2 months, 3months, 6months ,12months after CAR-T infusion | 
| Change of CAR Copies | CAR Copies measured by qPCR after CAR-T infusion | Days 4, 7, 10, 14 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion | 
| Change of CAR-T cell counts | CAR-T cell counts measured by Flow cytometry after CAR-T infusion | Days 4, 7, 10, 14 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion |