Acute Lymphocytic Leukemia
Conditions
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.
Interventions
BIOLOGICALLCAR-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.
Sponsors
Nanjing Legend Biotech Co.
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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: 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; \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 |
| 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 |
| 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 |
Countries
China
Outcome results
None listed