This study evaluates the safety and efficacy of novel ILT3-targeted CAR-T cell therapyfor patients with relapsed or refractory acute myeloid leukemia (M4/M5).
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.
Biological: anti-ILT3 CAR-T
Autologous T cells genetically modified with anti-ILT3 CAR
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.
Zhejiang Provincal People's Hospital
Hangzhou, Zhejiang, China
Investigator: Lai Jin
Contact: +86-18458227035
hjdl188@sina.com
Investigator: Jianping Lan
Lai Jin
+86-18458227035
hjdl188@sina.com
Jianping Lan, Principal Investigator
Zhejiang Provincial People's Hospital