Clinical trial NCT04803929: Clinical Study of Anti-ILT3 CAR-T Therapy for R/R AML(M4/M5)
Official title: Clinical Study of Autologous T Cells Modified With ILT3 Chimeric Antigen Receptor for Relapsed/Refractory Acute Myeloid Leukemia (M4/M5)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: AML M4
AML M5
Lead sponsor: Carbiogene Therapeutics Co. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Zhejiang Provincial People's Hospital
First posted: 2021-03-18
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of grade 3 or 4 treatment related adverse effects
timeFrame: up to 24 weeks after first infusion
measure: Implantation endpoint
timeFrame: up to 2 years after first infusion
Secondary outcomes:
measure: Disease specific response
timeFrame: up to 2 years after first infusion
measure: Overall survival
timeFrame: up to 2 years after inclusion
measure: Progress-free survival
timeFrame: up to 2 years after inclusion
measure: CAR-T residue
timeFrame: up to 2 years after first infusion
measure: Minimal residual disease (MRD)
timeFrame: up to 2 years after first infusion
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Provincal People's Hospital
state: Zhejiang
Study officials:
affiliation: Zhejiang Provincial People's Hospital
name: Jianping Lan
role: PRINCIPAL_INVESTIGATOR
References: