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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05654779
• Other study ID #: LB2202-0001
• Status: Terminated
• Phase: Phase 1
• Start date: December 12, 2022
• Est. completion date: September 26, 2023

Study information

• Verified date: November 2022
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 26, 2023
• Est. primary completion date: September 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

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 exclusion criteria)

• Previous gene therapy

• Previous anti CD33/CLL1 therapy

• Previous any target CAR-T cells therapy

3. Prior antitumor therapy with insufficient washout period;

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

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

6. Pregnant or breast-feeding women;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• LCAR-AMDR Cells Product
Subjects will receive a conditioning regimen before treatment with LCAR-AMDR cells

Locations

Country	Name	City	State
China	Beijing Gobroad BoRen Hospital	Beijing	Beijing
China	Chinese Academy of Medical Science and Blood Disease 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-AMDR infusion (Day 1)
Primary	Recommended Phase 2 dose (RP2D) finding	RP2D established through ATD+BOIN design	30 days after LCAR-AMDR 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-AMDR infusion	2 years after LCAR-AMDR 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-AMDR cell infusion	2 years after LCAR-AMDR 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-AMDR to the date of the first response evaluation of the subject who has met all criteria for CR or CRi.	2 years after LCAR-AMDR 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	Minimum 2 years after LCAR-AMDR infusion (Day 1)
Secondary	Event-free survival (EFS)	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	Minimum 2 years after LCAR-AMDR infusion (Day 1)
Secondary	Overall Survival (OS)	Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-AMDR to death of the subject	Minimum 2 years after LCAR-AMDR infusion (Day 1)
Secondary	The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative.	The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative.	Minimum 2 years after LCAR-AMDR infusion (Day 1)
Secondary	Incidence of anti-LCAR-AMDR antibody and positive sample titer	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	Minimum 2 years after LCAR-AMDR infusion (Day 1)