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

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphocytic Leukemia
• Intervention / Treatment: Biological: LCAR-AIO Cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jianxiang Wang Jianxiang Wang; Phone Number: 022-23909120; Email: wangjx@ihcams.ac.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing GoBroad Boren Hospital
      • Contact: Wu Tong; Phone Number: 1507109168486-10-83625200; Email: wut@gobroadhealthcare.com
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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;
2. Age 18-75 years;
3. ECOG score: 0-1;
4. Detect the expression of at least one of CD19/CD20/CD22 in leukemic cells by Flow cytometry in peripheral blood or bone marrow
5. Leukemia cells in the bone marrow >5%

6. Pathologically confirmed relapsed/refractory ALL must meet one of the following conditions:

   1. Naive patients who failed to achieve CR1 after standard chemotherapy;
   2. relapse within 12 months after CR1, or relapse after 12 months but fail to achieve CR2
   3. twice or more bone marrow relapse
   4. Philadelphia chromosomal positive (Ph+) and unable to tolerate TKI therapy, failed TKI therapy more than 2 lines, or had contraindications for TKI therapy
7. Clinical laboratory values meet screening visit criteria
8. 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;

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LCAR-AIO Cells; Each subject will be treated with LCAR-AIO Cells	Biological: LCAR-AIO Cells; 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.

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)]

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Collaborators: Nanjing Legend Biotech Co.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 14, 2022
• Primary Completion (ANTICIPATED): July 1, 2024
• Study Completion (ANTICIPATED): July 1, 2026

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (ACTUAL): March 23, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: BM2L202101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No