CLL-1/CD33 Targeted LCAR-AMDR Cells in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is a prospective, single-arm, open-label, single dose-finding and dose-expansion study that evaluates the safety, tolerability, PK, and anti-tumor efficacy of LCAR-AMDR cells in subjects with relapsed/refractory Acute Myeloid Leukemia who received adequate standard therapy.

Official Title
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A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of CLL1-/CD33 Targeted LCAR-AMDR Cells Product in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: LCAR-AMDR Cells Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject voluntarily participates in the clinical study; Fully understand and be Informed of the study and sign the Informed consent (Informed Consent Form, ICF)（For minors, the guardian shall also provide written informed consent ）; Willing to follow and able to complete all test procedures; Informed consent must be obtained before initiating any tests or procedures related to the study that are not part of the standard treatment of the subject's disease; Age 14-60 years; ECOG score: ≤2; Relapsed/refractory AML must meet one of the following conditions: Twice or more relapse; Newly diagnosed AML patients who failed after 2 cycles of standard chemotherapy; Relapse within 12 months after CR, or relapse after 12 months with CR but failed to respond to conventional chemotherapy; Persistent extramedullary leukemia. Meet the requirements of allogeneic HSCT Expected survival ≥ 3 months; Exclusion Criteria: Subject with APL/AML-M3:t(15;17)(q22;q12) Received any of the following treatments: Previous allo-HSCT(Subjects who received allo-HSCT for more than 6 months, have stopped immunosuppressive drugs and have no active GvHD are not included in the exclusion criteria) Previous gene therapy Previous anti CD33/CLL1 therapy Previous any target CAR-T cells therapy Prior antitumor therapy with insufficient washout period; CNS infiltration; Except for patients with prior CNS infiltration who are currently in remission; HBsAg, HBV DNA, HCV-Ab, HCV RNA or HIV-Ab positive; Pregnant or breast-feeding women;

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 60 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: LCAR-AMDR Cells Product<br>Each subject will be treated with LCAR-AMDR Cells | Biological: LCAR-AMDR Cells Product<br>* Subjects will receive a conditioning regimen before treatment with LCAR-AMDR cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity, and type of treatment-emergent adverse events (TEAEs) | An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment | Time Frame: Minimum 2 years after LCAR-AMDR infusion (Day 1) | 
| Recommended Phase 2 dose (RP2D) finding | RP2D established through ATD+BOIN design | 30 days after LCAR-AMDR infusion (Day 1) | 
| CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow | CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow after LCAR-AMDR infusion | 2 years after LCAR-AMDR infusion (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or CRi after treatment via LCAR-AMDR cell infusion | 2 years after LCAR-AMDR infusion (Day 1) | 
| Time to Response (TTR) | Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-AMDR to the date of the first response evaluation of the subject who has met all criteria for CR or CRi. | 2 years after LCAR-AMDR infusion (Day 1) | 
| Duration of Response (DoR) | Duration of Remission (DoR) is defined as the time from the first documentation of remission (CR or CRi) to the first documented relapse evidence of the responders | Minimum 2 years after LCAR-AMDR infusion (Day 1) | 
| Event-free survival (EFS) | Event-free survival (EFS) is defined as the time from the date of first infusion of the LCAR-AMDR to the first documented treatment failure, disease relapse or death (due to any cause), whichever occurs first | Minimum 2 years after LCAR-AMDR infusion (Day 1) | 
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AMDR to death of the subject | Minimum 2 years after LCAR-AMDR infusion (Day 1) | 
| The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative. | The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative. | Minimum 2 years after LCAR-AMDR infusion (Day 1) | 
| Incidence of anti-LCAR-AMDR antibody and positive sample titer | Venous blood samples will be collected to measure LCAR-AMDR positive cell concentrations and the transgenic level of LCAR-AMDR, at the time points when anti-LCAR-AMDR antibody serum samples are evaluated | Minimum 2 years after LCAR-AMDR infusion (Day 1) |