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

Acute Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05292898
• Other study ID #: BM2L202101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 14, 2022
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: July 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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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Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
China	Beijing Gobroad BoRen Hospital	Beijing	Beijing
China	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital, China	Nanjing Legend Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)]
Primary	Recommended Phase 2 dose (RP2D) finding	RP2D established through ATD+BOIN design	[Time Frame: 30 days after LCAR-AIO infusion (Day 1)]
Primary	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	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)]
Secondary	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)]
Secondary	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)]
Secondary	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)]
Secondary	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)]
Secondary	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)]