Clinical trial NCT05463640: Evaluate the Safety and Efficacy of ADGRE2 CAR-T in Patients With R/R AML
Official title: To Evaluate the Safety and Efficacy of ADGRE2 CAR-T in Patients With Relapsed and Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: AML
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2022-07-19
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Changes in cytokine level after ADGRE2 CAR-T infusion.
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion.
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
Secondary outcomes:
measure: Complete response rate(CRR)
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: Partial response Rate (PRR)
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: Overall response Rate(ORR)
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
Other outcomes:
measure: Overall survival
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: Recurrence free survival (RFS)
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: Event-free survival (EFS)
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: MRD negative rate
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: Median BM Reduction
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
measure: Percentage of subjects disengaged from transfusion
timeFrame: Up to 2 years after ADGRE2 CAR-T infusion
Locations:
city: Hangzhou
country: China
facility: Mingming Zhang Zhang
Study officials:
affiliation: The first hospital affiliated Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: