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

Clinical Study of Autologous T Cells Modified With ILT3 Chimeric Antigen Receptor for Relapsed/Refractory Acute Myeloid Leukemia (M4/M5)

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).

Study Overview

• Status: Recruiting
• Conditions: AML M5; AML M4
• Intervention / Treatment: Biological: anti-ILT3 CAR-T

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.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Lai Jin; Phone Number: +86-18458227035; Email: hjdl188@sina.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincal People's Hospital
      • Contact: Lai Jin; Phone Number: +86-18458227035; Email: hjdl188@sina.com
      • Principal Investigator: Jianping Lan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-ILT3 CAR-T cells; All subjects were intravenous administrated with anti-ILT3 CAR-T cells	Biological: anti-ILT3 CAR-T; Autologous T cells genetically modified with anti-ILT3 CAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of grade 3 or 4 treatment related adverse effects	All the CAR-T treatment related adverse events，including Dose limiting toxicity (DLT), cytokine release syndrome (CRS), CAR-T associated encephalopathy syndrome, will be assessed and graded by NCI CTCAE v 5.0.	up to 24 weeks after first infusion
Implantation endpoint	To assess the duration of CAR-positive T cells in circulation, the copy number of CAR DNA was measured at the preset follow-up time point. The time when the results of any two consecutive tests were negative, were recorded as the "implantation endpoint"	up to 2 years after first infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease specific response	Disease specific response includes, but are not limited to, complete response (CR) including morphological leukemia-free status, morphological CR, cytogenetic CR, molecular CR, and partial response (PR).	up to 2 years after first infusion
Overall survival	From date of inclusion to date of progression, relapse, or death from any cause	up to 2 years after inclusion
Progress-free survival	The length of time that a participant's disease did not progress during and after CAR-T treatment	up to 2 years after inclusion
CAR-T residue	The residue of CAR-positive T cells in circulation determined by flow cytometry	up to 2 years after first infusion
Minimal residual disease (MRD)	MRD is a status that none tumor cells can be detected by standard cell morphology.	up to 2 years after first infusion

Collaborators and Investigators

• Sponsor: Carbiogene Therapeutics Co. Ltd.
• Collaborators: Zhejiang Provincial People's Hospital
• Investigators: Principal Investigator: Jianping Lan, Zhejiang Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 2021KY014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No