Evaluate the Safety and Efficacy of CLL1+CD33 CAR-T in Patients With R/R AML

Study Overview
=================
Brief Summary
-----------------
This is an open label, phase I study to assess the safety and efficacy of CLL1+CD33 CAR-T in patients with relapsed and refractory acute myeloid leukemia

Official Title
-----------------
To Evaluate the Safety and Efficacy of CLL1+CD33 CAR-T in Patients With Relapsed and Refractory Acute Myeloid Leukemia

Conditions
-----------------
AML

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities; Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML); The expression of CLL1 and CD33 in AML blast is positive ; The patient has recovered from the toxicity of previous treatment; ECOG score ≤ 2 and expected survival period is not less than 3 months; Adequate organ function defined as: AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen saturation ≥92%; LVEF≥45%; Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test; From the use of study drug to 2 years after treatment, males and female of childbearing potential must agree to use an effective method of contraception Exclusion Criteria: Diagnosis of acute promyelocytic leukemia; History or presence of a CNS disorder; HBsAg or HBcAb are positive; HCV 、HIV and Syphilis antibody are positive, CMV DNA in peripheral blood is more than≥500 copies /mL; History of severe hypersensitivity reaction; History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment; History of organ transplant surgery; Required systemic application of immunosuppressive or other drugs; Auto-SCT within the 3 months before enrollment; Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES)); Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) ; Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management; Live vaccine received within the ≤ 4 weeks before enrollment; Persons with serious mental illness; History of major surgical operations four weeks before enrollment; History of alcoholism or substance abuse; Was identified by the investigators as unsuitable to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 70 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: CLL1+CD33 CAR-T<br>Dose Escalation:After enrollment ,Participants complete the PBMC apheresis,then complete the Lymphocyte clearance,and then receive the dose climning test: 3×10e6/kg，6 ×10e6/kg，9×10e6/kg. Dose Expansion:Participants receive a single dose (at the MTD determined). | Biological: CLL1+CD33 CAR-T<br>* CLL1+CD33 CAR-T is a new type CAR-T cells therapy for patients with acute myeloid leukemia.<br>|

What is the study measuring?
-----------------
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. Cytokines include IL-2、IL-6、IFN-γ. | Up to 2 years after CLL1+CD33 CAR-T infusion | 
| The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion. | Track CAR-T cells expansion in patients after infusion by flow cytometry and qPCR. | Up to 2 years after CLL1+CD33 CAR-T infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate(CRR) | Proportion of subjects who achieved morphological complete response (CR) and complete response with hematologic incomplete recovery (CRi) | Up to 2 years after CLL1+CD33 CAR-T infusion | 
| Partial response Rate (PRR) | Proportion of subjects who achieved a partial response (PR) | Up to 2 years after CLL1+CD33 CAR-T infusion | 
| Overall response Rate(ORR) | Proportion of subjects who achieved CR, CRi, or PR | Up to 2 years after CLL1+CD33 CAR-T infusion |