Clinical trial NCT05654779: CLL-1/CD33 Targeted LCAR-AMDR Cells in Patients With Relapsed or Refractory Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2022-12-16
Enrollment: 4
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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;

Primary outcomes:
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: Time Frame: Minimum 2 years after LCAR-AMDR infusion (Day 1)
measure: Recommended Phase 2 dose (RP2D) finding
timeFrame: 30 days after LCAR-AMDR infusion (Day 1)
measure: CAR positive T cells and CAR transgene levels in peripheral blood and bone marrow
timeFrame: 2 years after LCAR-AMDR infusion (Day 1)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 2 years after LCAR-AMDR infusion (Day 1)
measure: Time to Response (TTR)
timeFrame: 2 years after LCAR-AMDR infusion (Day 1)
measure: Duration of Response (DoR)
timeFrame: Minimum 2 years after LCAR-AMDR infusion (Day 1)
measure: Event-free survival (EFS)
timeFrame: Minimum 2 years after LCAR-AMDR infusion (Day 1)
measure: Overall Survival (OS)
timeFrame: Minimum 2 years after LCAR-AMDR infusion (Day 1)
measure: The proportion of subjects who achieve CR or Cri and obtain bone marrow MRD negative.
timeFrame: Minimum 2 years after LCAR-AMDR infusion (Day 1)
measure: Incidence of anti-LCAR-AMDR antibody and positive sample titer
timeFrame: Minimum 2 years after LCAR-AMDR infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad BoRen Hospital
state: Beijing
city: Tianjin
country: China
facility: Chinese Academy of Medical Science and Blood Disease Hospital
state: Tianjin
Study officials:
References: