Evaluate the Safety and Efficacy of ADGRE2 CAR-T in Patients With R/R AML

Phase 1

Not yet recruiting

• Conditions: AML
• Interventions: Biological: ADGRE2 CAR-T

• Registration Number: NCT05463640
• Lead Sponsor: Zhejiang University

Brief Summary

This is an open label, phase I study to assess the safety and efficacy of ADGRE2 CAR-T in patients with relapsed and refractory acute myeloid leukemia

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-07
• Study First Submitted: 2022-07-01
• Study First Submitted QC: 2022-07-17
• Last Update Submitted: 2022-07-17
• Study First Posted: 2022-07-19
• Last Update Posted: 2022-07-19
• Study Start: 2022-08-02
• Primary Completion: 2024-08-02
• Study Completion: 2025-08-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities;

2. Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML);

3. The expression of ADGRE2 in AML blast is positive ;

4. The patient has recovered from the toxicity of previous treatment;

5. ECOG score ≤ 2 and expected survival period is not less than 3 months;

6. Adequate organ function defined as:

   AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen saturation ≥92%; LVEF≥45%;

7. Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test;

8. From the use of study drug to 2 years after treatment, males and female of childbearing potential must agree to use an effective method of contraception

Exclusion Criteria

1. Diagnosis of acute promyelocytic leukemia;
2. History or presence of a CNS disorder;
3. HBsAg or HBcAb are positive; HCV 、HIV and Syphilis antibody are positive, CMV DNA in peripheral blood is more than≥500 copies /mL;
4. History of severe hypersensitivity reaction;
5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment;
6. History of organ transplant surgery;
7. Required systemic application of immunosuppressive or other drugs;
8. Auto-SCT within the 3 months before enrollment;
9. Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES));
10. Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) ;
11. Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management;
12. Live vaccine received within the ≤ 4 weeks before enrollment;
13. Persons with serious mental illness;
14. History of major surgical operations four weeks before enrollment;
15. History of alcoholism or substance abuse;
16. Was identified by the investigators as unsuitable to participate in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ADGRE2 CAR-T	ADGRE2 CAR-T	Dose Escalation:After enrollment ,Participants complete the PBMC apheresis,then complete the Lymphocyte clearance,and then receive the dose climning test: 3×10e6/kg，6 ×10e6/kg，9×10e6/kg. Dose Expansion:Participants receive a single dose (at the MTD determined).

Primary Outcome Measures

Name	Time	Method
Changes in cytokine level after ADGRE2 CAR-T infusion.	Up to 2 years after ADGRE2 CAR-T infusion	Calculate the change of cytokine level in peripheral blood by flow cytometry after CAR-T infusion. Cytokines include IL-2、IL-6、TNF-α、IFN-γ.
The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion.	Up to 2 years after ADGRE2 CAR-T infusion	Track CAR-T cells expansion in patients after infusion by flow cytometry and qPCR.

Secondary Outcome Measures

Name	Time	Method
Overall response Rate(ORR)	Up to 2 years after ADGRE2 CAR-T infusion	Proportion of subjects who achieved CR, CRi, or PR
Complete response rate(CRR)	Up to 2 years after ADGRE2 CAR-T infusion	Proportion of subjects who achieved morphological complete response (CR) and complete response with hematologic incomplete recovery (CRi)
Partial response Rate (PRR)	Up to 2 years after ADGRE2 CAR-T infusion	Proportion of subjects who achieved a partial response (PR)

Trial Locations

Locations (1)

Mingming Zhang Zhang; 🇨🇳 Hangzhou, China