Clinical Study of Anti-ILT3 CAR-T Therapy for R/R AML(M4/M5)

Carbiogene Therapeutics

Status and phase: Enrolling; Early Phase 1

Conditions: AML M5; AML M4

Treatments: Biological: anti-ILT3 CAR-T

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04803929

2021KY014

Details and patient eligibility

About

This study evaluates the safety and efficacy of novel ILT3-targeted CAR-T cell therapy for patients with relapsed or refractory acute myeloid leukemia (M4/M5).

Full description

Our group has developed a novel anti-ILT3 CAR T cell therapy, and this pilot study is focused on the safety and efficacy of the anti-ILT3 CAR-T for R/R AML(M4/M5) patients. A total of 25 subjects are intravenously adminstered with anti-ILT3 CAR-T cells. The dosages of CAR-T cells follow the "3+3" dose increment program.

Enrollment: 25 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female patients, aged ≥18 years or ≤70 years;

2. Acute myeloid leukemia AML M4/M5 subtype was diagnosed according to Fab standard classification, confirmed by bone marrow IHC or ILT3-positive expression by flow cytometry in monocytes (primary and young monocytes in bone marrow ≥20%)

3. Relapsed/refractory patients, whose conditions meet:

   • Recurrent AML diagnosis standard: complete remission (CR) after the original cells in peripheral blood again leukemia cells or bone marrow > 0.050 (with the exception of consolidation chemotherapy after bone marrow regeneration for other reasons) or myeloid leukemia cells infiltrating outside.
   • Refractory AML diagnostic criteria: after two standard regimen for treatment invalid early cure; patients who relapsed within 12 months after consolidation and intensive treatment after CR; relapsed after 12 months but failed to respond to conventional chemotherapy; 2 or more recurrences; patients with persistent extramedullary leukemia.

4. Main organ functions meet the following conditions:

   • Kidney function: creatinine clearance (absolute value) or 60 ml/min or creatinine < 2.0 mg/dl or < 2 times the subjects' age group upper limit of normal (ULN) blood.
   • Liver function: ALT ≤ 3 or less ULN, AST ≤ 3 or less ULN.
   • Heart function: the ejection fraction ≥ 50%, measured by echocardiography (ECHO) or more acquisition scan (MUGA).
   • Lung function: no clinical significance of pleural effusion, baseline blood oxygen saturation > 92%.

5. ECOG physical status score 0-3.

6. No use of steroid hormones within 2 weeks.

7. Sufficient venous access to single or venous blood collection is available, and there are no other contraindications to blood cell separation.

8. Signed written informed consent form.

Exclusion criteria

Subjects will not be included in the study if they meet any of the following criteria:

1. Pregnant or lactating women;

2. HIV serological positive;

3. Active bacterial, fungal or viral infections that are not controlled by treatment;

4. Suffer from coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage or other serious cardiovascular and cerebrovascular diseases;

5. History and concomitant diseases:

   • Subjects with known or suspected autoimmune diseases or immunodeficiency diseases;
   • Subjects requiring systemic treatment with corticosteroids or other immunosuppressive agents during treatment;
   • Subjects who have previously received other gene therapies;
   • Subjects with a history of organ transplantation (referring to solid organ transplantation);
   • Subjects with severe mental disorders;
   • Participated in other clinical studies within one month before the collection of PBMC;
   • Uncontrolled active hepatitis B and/or C infection (hepatitis B: HBV DNA > 500 IU/ml or copy number > 2500 copies /ml;
   • Hepatitis C: HCV antibody positive and HCV-RNA levels above the detection limit);
   • Any serious or uncontrolled disease that the Investigator considers to be likely to increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive the study drug;
   • Subjects who underwent major surgery or suffered significant trauma within 4 weeks prior to the collection of PBMCs, or who are expected to require major surgery during the study period.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Anti-ILT3 CAR-T cells

Experimental group

Description:

All subjects were intravenous administrated with anti-ILT3 CAR-T cells

Treatment:

Biological: anti-ILT3 CAR-T