Acute Myeloid Leukemia
Conditions
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.
Interventions
BIOLOGICALLCAR-AMDR Cells Product
Subjects will receive a conditioning regimen before treatment with LCAR-AMDR cells
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Nanjing Legend Biotech Co.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. 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; 2. Age 14-60 years; 3. ECOG score: ≤2; 4. Relapsed/refractory AML must meet one of the following conditions: 1. Twice or more relapse; 2. Newly diagnosed AML patients who failed after 2 cycles of standard chemotherapy; 3. Relapse within 12 months after CR, or relapse after 12 months with CR but failed to respond to conventional chemotherapy; 4. Persistent extramedullary leukemia. 5. Meet the requirements of allogeneic HSCT 6. Expected survival ≥ 3 months;
Exclusion criteria
1. Subject with APL/AML-M3:t(15;17)(q22;q12) 2. Received any of the following treatments: * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Outcome results
None listed