CLL-1/CD33 Targeted LCAR-AMDR Cells in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Sponsor
Institute of Hematology & Blood Diseases Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05654779
Collaborator
Nanjing Legend Biotech Co. (Industry)
34
2
1
49.7
17
0.3

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
  • Biological: LCAR-AMDR Cells Product
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
34 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of CLL1-/CD33 Targeted LCAR-AMDR Cells Product in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date :
Dec 12, 2022
Anticipated Primary Completion Date :
Feb 1, 2025
Anticipated Study Completion Date :
Feb 1, 2027

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. 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

  2. Recommended Phase 2 dose (RP2D) finding [30 days after LCAR-AMDR infusion (Day 1)]

    RP2D established through ATD+BOIN design

  3. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

Ages Eligible for Study:
14 Years to 60 Years
Sexes Eligible for Study:
All
Accepts 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:

  5. Twice or more relapse;

  6. Newly diagnosed AML patients who failed after 2 cycles of standard chemotherapy;

  7. Relapse within 12 months after CR, or relapse after 12 months with CR but failed to respond to conventional chemotherapy;

  8. Persistent extramedullary leukemia.

  9. Meet the requirements of allogeneic HSCT

  10. 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 exclusion criteria)

  • Previous gene therapy

  • Previous anti CD33/CLL1 therapy

  • Previous any target CAR-T cells therapy

  1. Prior antitumor therapy with insufficient washout period;

  2. CNS infiltration; Except for patients with prior CNS infiltration who are currently in remission;

  3. HBsAg, HBV DNA, HCV-Ab, HCV RNA or HIV-Ab positive;

  4. Pregnant or breast-feeding women;

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov Identifier:
NCT05654779
Other Study ID Numbers:
  • LB2202-0001
First Posted:
Dec 16, 2022
Last Update Posted:
Jan 31, 2023
Last Verified:
Nov 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 31, 2023