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

AML Clinical Trial

Official title:

To Evaluate the Safety and Efficacy of ADGRE2 CAR-T in Patients With Relapsed and Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05463640
• Other study ID #: BG-CT-22-002(ADGRE2)
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 2, 2022
• Est. completion date: August 2, 2025

Study information

• Verified date: July 2022
• Source: Zhejiang University
• Contact: Mingming Zhang, MD
• Phone: 13656674208
• Email: mingmingzhang[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: August 2, 2025
• Est. primary completion date: August 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• AML

Intervention

Biological:
• ADGRE2 CAR-T
ADGRE2 CAR-T is a new type CAR-T cells therapy for patients with acute myeloid leukemia.

Locations

Country	Name	City	State
China	Mingming Zhang Zhang	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival	Death from any cause from the beginning of cell transfusion	Up to 2 years after ADGRE2 CAR-T infusion
Other	Recurrence free survival (RFS)	From remission to relapse or death of the subject (including all causes), whether the subject relapsed or died is unknown until the date of the last follow-up examination.	Up to 2 years after ADGRE2 CAR-T infusion
Other	Event-free survival (EFS)	Counting from the beginning of cell transfusion until treatment failure, recurrence, or death (various causes). Subjects without any of these events were counted up to the last follow-up examination date. For patients without CR or CRi, EFS is calculated from the beginning of cell transfusion until disease progression or death. Based on the initial event.	Up to 2 years after ADGRE2 CAR-T infusion
Other	MRD negative rate	The rate of MRD negative subjects was determined by flow cytometry.	Up to 2 years after ADGRE2 CAR-T infusion
Other	Median BM Reduction	Changes of bone marrow primitive cells after cell transfusion from baseline.	Up to 2 years after ADGRE2 CAR-T infusion
Other	Percentage of subjects disengaged from transfusion	Percentage of baseline transfusion-dependent subjects who were discharged from transfusion after cell transfusion.	Up to 2 years after ADGRE2 CAR-T infusion
Primary	Changes in cytokine level 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-a?IFN-?.	Up to 2 years after ADGRE2 CAR-T infusion
Primary	The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion.	Track CAR-T cells expansion in patients after infusion by flow cytometry and qPCR.	Up to 2 years after ADGRE2 CAR-T infusion
Secondary	Complete response rate(CRR)	Proportion of subjects who achieved morphological complete response (CR) and complete response with hematologic incomplete recovery (CRi)	Up to 2 years after ADGRE2 CAR-T infusion
Secondary	Partial response Rate (PRR)	Proportion of subjects who achieved a partial response (PR)	Up to 2 years after ADGRE2 CAR-T infusion
Secondary	Overall response Rate(ORR)	Proportion of subjects who achieved CR, CRi, or PR	Up to 2 years after ADGRE2 CAR-T infusion