A Triple-targeted Cell Preparation Targeting CD19/CD20/CD22 in Patients With Relapsed/Refractory B-cell Acute Lymphocytic Leukemia

Study Overview
=================
Brief Summary
-----------------
A phase I, open-label clinical study to evaluate the safety, tolerability, and efficacy of LCAR-AIO, a triple-targeted cell preparation targeting CD19/CD20/CD22, in patients with relapsed/refractory B-cell acute lymphocytic leukemia

Detailed Description
-----------------
This is an open-label, dose escalation/expansion study to assess the safety, tolerability, and efficacy of LCAR-AIO in patients ≥ 18 years of age with relapsed or refractory B-cell acute lymphocytic leukemia. Patients who meet the eligibility criteria will receive a single dose of LCAR-AIO infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up.

Official Title
-----------------
A Phase I, Open-label Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-AIO, a Triple-targeted Cell Preparation Targeting CD19/CD20/CD22, in Patients With Relapsed/Refractory B-cell Acute Lymphocytic Leukemia

Conditions
-----------------
Acute Lymphocytic Leukemia

Intervention / Treatment
-----------------
* Biological: LCAR-AIO Cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent; Age 18-75 years; ECOG score: 0-1; Detect the expression of at least one of CD19/CD20/CD22 in leukemic cells by Flow cytometry in peripheral blood or bone marrow Leukemia cells in the bone marrow >5% Pathologically confirmed relapsed/refractory ALL must meet one of the following conditions: Naive patients who failed to achieve CR1 after standard chemotherapy; relapse within 12 months after CR1, or relapse after 12 months but fail to achieve CR2 twice or more bone marrow relapse Philadelphia chromosomal positive (Ph+) and unable to tolerate TKI therapy, failed TKI therapy more than 2 lines, or had contraindications for TKI therapy Clinical laboratory values meet screening visit criteria Expected survival ≥ 3 months; Exclusion Criteria: 1.Prior antitumor therapy with insufficient washout period; 2.CNS infiltration; Except for patients with prior CNS infiltration who are currently in remission; 3.Have received two or more targets (CD19/CD20/CD22) CAR-T cell therapy (including but not limited to sequential infusion) at any previous time, or have received CAR-T cell therapy from Camel family origin; 4.With acute or chronic graft-versus-host disease; 5.Isolated extramedullary relapse, but hepatic, spleen, or lymph node-isolated extramedullary relapse is acceptable; 6.HBsAg, HBV DNA, HCV-Ab, HCV RNA or HIV-Ab positive; 7.Pregnant or lactating women; -

Ages Eligible for Study
-----------------
Minimum Age: 18 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: LCAR-AIO Cells<br>Each subject will be treated with LCAR-AIO Cells | Biological: LCAR-AIO Cells<br>* LCAR-AIO Cells before treatment with LCAR-AIO cells, subjects will receive a conditioning regimen (IV infusion of cyclophosphamide 300 mg/m^2 and fludarabine 30mg/m^2 once daily (QD) for 3 days.<br>|

What is the study measuring?
-----------------
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-AIO infusion (Day 1)] | 
| Recommended Phase 2 dose (RP2D) finding | RP2D established through ATD+BOIN design | [Time Frame: 30 days after LCAR-AIO 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-AIO infusion | [Time Frame: 2 years after LCAR-AIO 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-AIO cell infusion | [Time Frame: 90 days after LCAR-AIO infusion (Day 1)] | 
| Time to Response (TTR) | Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-AIO to the date of the first response evaluation of the subject who has met all criteria for CR or CRi. | [Time Frame: 90 days after LCAR-AIO 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 | [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)] | 
| Relapse-free survival (RFS) | Relapse-free survival (RFS) is defined as the time from the date of first infusion of the LCAR-AIO to the first documented disease relapse or death (due to any cause), whichever occurs first | [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)] | 
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AIO to death of the subject | [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)] | 
| Incidence of anti-LCAR-AIO antibody and positive sample titer | Venous blood samples will be collected to measure LCAR-AIO positive cell concentrations and the transgenic level of LCAR-H93T, at the time points when anti-LCAR-AIO antibody serum samples are evaluated | [Time Frame: Minimum 2 years after LCAR-H93T infusion (Day 1)] |