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

Sponsor
Institute of Hematology & Blood Diseases Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05292898
Collaborator
Nanjing Legend Biotech Co. (Industry)
34
2
1
51.6
17
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Study Details

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

Condition or Disease Intervention/Treatment Phase
  • Biological: LCAR-AIO Cells
Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
34 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 14, 2022
Anticipated Primary Completion Date :
Jul 1, 2024
Anticipated Study Completion Date :
Jul 1, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Incidence, severity, and type of treatment-emergent adverse events (TEAEs) [[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]]

    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

  2. Recommended Phase 2 dose (RP2D) finding [[Time Frame: 30 days after LCAR-AIO infusion (Day 1)]]

    RP2D established through ATD+BOIN design

  3. CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow [[Time Frame: 2 years after LCAR-AIO infusion (Day 1)]]

    CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow after LCAR-AIO infusion

Secondary Outcome Measures

  1. Overall response rate (ORR) [[Time Frame: 90 days after LCAR-AIO infusion (Day 1)]]

    Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or CRi after treatment via LCAR-AIO cell infusion

  2. Time to Response (TTR) [[Time Frame: 90 days after LCAR-AIO infusion (Day 1)]]

    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.

  3. Duration of Response (DoR) [[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]]

    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

  4. Relapse-free survival (RFS) [[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]]

    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

  5. Overall Survival (OS) [[Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]]

    Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AIO to death of the subject

  6. Incidence of anti-LCAR-AIO antibody and positive sample titer [[Time Frame: Minimum 2 years after LCAR-H93T infusion (Day 1)]]

    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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:

  7. Naive patients who failed to achieve CR1 after standard chemotherapy;

  8. relapse within 12 months after CR1, or relapse after 12 months but fail to achieve CR2

  9. twice or more bone marrow relapse

  10. Philadelphia chromosomal positive (Ph+) and unable to tolerate TKI therapy, failed TKI therapy more than 2 lines, or had contraindications for TKI therapy

  11. Clinical laboratory values meet screening visit criteria

  12. 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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Contacts and Locations

Locations

Site City State Country Postal Code
1 Beijing Gobroad BoRen Hospital Beijing Beijing China
2 Institute of Hematology & Blood Diseases Hospital Tianjin Tianjin China

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov Identifier:
NCT05292898
Other Study ID Numbers:
  • BM2L202101
First Posted:
Mar 23, 2022
Last Update Posted:
Jun 1, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 1, 2022