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

Primary Purpose

Acute Lymphocytic Leukemia

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LCAR-AIO Cells
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphocytic Leukemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

-

Sites / Locations

  • Beijing Gobroad BoRen HospitalRecruiting
  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LCAR-AIO Cells

Arm Description

Each subject will be treated with LCAR-AIO Cells

Outcomes

Primary Outcome Measures

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
Recommended Phase 2 dose (RP2D) finding
RP2D established through ATD+BOIN design
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

Secondary Outcome Measures

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 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.
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
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
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
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

Full Information

First Posted
March 14, 2022
Last Updated
May 31, 2022
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Nanjing Legend Biotech Co.
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1. Study Identification

Unique Protocol Identification Number
NCT05292898
Brief Title
A Triple-targeted Cell Preparation Targeting CD19/CD20/CD22 in Patients With Relapsed/Refractory B-cell Acute Lymphocytic Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2022 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Nanjing Legend Biotech Co.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LCAR-AIO Cells
Arm Type
Experimental
Arm Description
Each subject will be treated with LCAR-AIO Cells
Intervention Type
Biological
Intervention Name(s)
LCAR-AIO Cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
Description
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
[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Title
Recommended Phase 2 dose (RP2D) finding
Description
RP2D established through ATD+BOIN design
Time Frame
[Time Frame: 30 days after LCAR-AIO infusion (Day 1)]
Title
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow
Description
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow after LCAR-AIO infusion
Time Frame
[Time Frame: 2 years after LCAR-AIO infusion (Day 1)]
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
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
[Time Frame: 90 days after LCAR-AIO infusion (Day 1)]
Title
Time to Response (TTR)
Description
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
[Time Frame: 90 days after LCAR-AIO infusion (Day 1)]
Title
Duration of Response (DoR)
Description
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
[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Title
Relapse-free survival (RFS)
Description
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
[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Title
Overall Survival (OS)
Description
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AIO to death of the subject
Time Frame
[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
Title
Incidence of anti-LCAR-AIO antibody and positive sample titer
Description
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
[Time Frame: Minimum 2 years after LCAR-H93T infusion (Day 1)]

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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; -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianxiang Wang Jianxiang Wang
Phone
022-23909120
Email
wangjx@ihcams.ac.cn
Facility Information:
Facility Name
Beijing Gobroad BoRen Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wu Tong
Phone
1507109168486-10-83625200
Email
wut@gobroadhealthcare.com
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wang Jianxiang
Phone
022-23909120
Email
wangjx@ihcams.ac.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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