A Triple-targeted Cell Preparation Targeting CD19/CD20/CD22 in Patients With Relapsed/Refractory B-cell Acute Lymphocytic Leukemia
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 |
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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Outcome Measures
Primary Outcome Measures
- 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
- Recommended Phase 2 dose (RP2D) finding [[Time Frame: 30 days after LCAR-AIO infusion (Day 1)]]
RP2D established through ATD+BOIN design
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
Inclusion Criteria:
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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;
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Age 18-75 years;
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ECOG score: 0-1;
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Detect the expression of at least one of CD19/CD20/CD22 in leukemic cells by Flow cytometry in peripheral blood or bone marrow
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Leukemia cells in the bone marrow >5%
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Pathologically confirmed relapsed/refractory ALL must meet one of the following conditions:
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Naive patients who failed to achieve CR1 after standard chemotherapy;
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relapse within 12 months after CR1, or relapse after 12 months but fail to achieve CR2
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twice or more bone marrow relapse
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Philadelphia chromosomal positive (Ph+) and unable to tolerate TKI therapy, failed TKI therapy more than 2 lines, or had contraindications for TKI therapy
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Clinical laboratory values meet screening visit criteria
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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 | |
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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.- BM2L202101