Clinical trial NCT05292898: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Lymphocytic Leukemia
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2022-03-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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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Primary outcomes:
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
measure: Recommended Phase 2 dose (RP2D) finding
timeFrame: [Time Frame: 30 days after LCAR-AIO infusion (Day 1)]
measure: CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow
timeFrame: [Time Frame: 2 years after LCAR-AIO infusion (Day 1)]
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: [Time Frame: 90 days after LCAR-AIO infusion (Day 1)]
measure: Time to Response (TTR)
timeFrame: [Time Frame: 90 days after LCAR-AIO infusion (Day 1)]
measure: Duration of Response (DoR)
timeFrame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
measure: Relapse-free survival (RFS)
timeFrame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
measure: Overall Survival (OS)
timeFrame: [Time Frame: Minimum 2 years after LCAR-AIO infusion (Day 1)]
measure: Incidence of anti-LCAR-AIO antibody and positive sample titer
timeFrame: [Time Frame: Minimum 2 years after LCAR-H93T infusion (Day 1)]
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad BoRen Hospital
state: Beijing
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
References: