CLL-1/CD33 Targeted LCAR-AMDR Cells in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Details
Study Description
Brief Summary
This is a prospective, single-arm, open-label, single dose-finding and dose-expansion study that evaluates the safety, tolerability, PK, and anti-tumor efficacy of LCAR-AMDR cells in subjects with relapsed/refractory Acute Myeloid Leukemia who received adequate standard therapy.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: LCAR-AMDR Cells Product Each subject will be treated with LCAR-AMDR Cells |
Biological: LCAR-AMDR Cells Product
Subjects will receive a conditioning regimen before treatment with LCAR-AMDR cells
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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-AMDR 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 [30 days after LCAR-AMDR infusion (Day 1)]
RP2D established through ATD+BOIN design
- CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow [2 years after LCAR-AMDR infusion (Day 1)]
CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow after LCAR-AMDR infusion
Secondary Outcome Measures
- Overall response rate (ORR) [2 years after LCAR-AMDR infusion (Day 1)]
Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or CRi after treatment via LCAR-AMDR cell infusion
- Time to Response (TTR) [2 years after LCAR-AMDR infusion (Day 1)]
Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-AMDR to the date of the first response evaluation of the subject who has met all criteria for CR or CRi.
- Duration of Response (DoR) [Minimum 2 years after LCAR-AMDR 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
- Event-free survival (EFS) [Minimum 2 years after LCAR-AMDR infusion (Day 1)]
Event-free survival (EFS) is defined as the time from the date of first infusion of the LCAR-AMDR to the first documented treatment failure, disease relapse or death (due to any cause), whichever occurs first
- Overall Survival (OS) [Minimum 2 years after LCAR-AMDR infusion (Day 1)]
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AMDR to death of the subject
- The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative. [Minimum 2 years after LCAR-AMDR infusion (Day 1)]
The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative.
- Incidence of anti-LCAR-AMDR antibody and positive sample titer [Minimum 2 years after LCAR-AMDR infusion (Day 1)]
Venous blood samples will be collected to measure LCAR-AMDR positive cell concentrations and the transgenic level of LCAR-AMDR, at the time points when anti-LCAR-AMDR antibody serum samples are evaluated
Eligibility Criteria
Criteria
Inclusion Criteria:
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The subject voluntarily participates in the clinical study; Fully understand and be Informed of the study and sign the Informed consent (Informed Consent Form, ICF)(For minors, the guardian shall also provide written informed consent ); Willing to follow and able to complete all test procedures; Informed consent must be obtained before initiating any tests or procedures related to the study that are not part of the standard treatment of the subject's disease;
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Age 14-60 years;
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ECOG score: ≤2;
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Relapsed/refractory AML must meet one of the following conditions:
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Twice or more relapse;
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Newly diagnosed AML patients who failed after 2 cycles of standard chemotherapy;
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Relapse within 12 months after CR, or relapse after 12 months with CR but failed to respond to conventional chemotherapy;
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Persistent extramedullary leukemia.
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Meet the requirements of allogeneic HSCT
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Expected survival ≥ 3 months;
Exclusion Criteria:
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Subject with APL/AML-M3:t(15;17)(q22;q12)
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Received any of the following treatments:
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Previous allo-HSCT(Subjects who received allo-HSCT for more than 6 months, have stopped immunosuppressive drugs and have no active GvHD are not included in the exclusion criteria)
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Previous gene therapy
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Previous anti CD33/CLL1 therapy
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Previous any target CAR-T cells therapy
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Prior antitumor therapy with insufficient washout period;
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CNS infiltration; Except for patients with prior CNS infiltration who are currently in remission;
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HBsAg, HBV DNA, HCV-Ab, HCV RNA or HIV-Ab positive;
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Pregnant or breast-feeding women;
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Beijing Gobroad BoRen Hospital | Beijing | Beijing | China | 100070 |
2 | Chinese Academy of Medical Science and Blood Disease Hospital | Tianjin | Tianjin | China | 300020 |
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.- LB2202-0001