AML
Conditions
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
Interventions
BIOLOGICALADGRE2 CAR-T
ADGRE2 CAR-T is a new type CAR-T cells therapy for patients with acute myeloid leukemia.
Sponsors
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Overall response Rate(ORR) | Up to 2 years after ADGRE2 CAR-T infusion | Proportion of subjects who achieved CR, CRi, or PR |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 2 years after ADGRE2 CAR-T infusion | Death from any cause from the beginning of cell transfusion |
| Percentage of subjects disengaged from transfusion | Up to 2 years after ADGRE2 CAR-T infusion | Percentage of baseline transfusion-dependent subjects who were discharged from transfusion after cell transfusion. |
| Recurrence free survival (RFS) | Up to 2 years after ADGRE2 CAR-T infusion | 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. |
| Event-free survival (EFS) | Up to 2 years after ADGRE2 CAR-T infusion | 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. |
| MRD negative rate | Up to 2 years after ADGRE2 CAR-T infusion | The rate of MRD negative subjects was determined by flow cytometry. |
| Median BM Reduction | Up to 2 years after ADGRE2 CAR-T infusion | Changes of bone marrow primitive cells after cell transfusion from baseline. |
Countries
China
Contacts
Primary ContactMingming Zhang, MD
Backup ContactHe Huang, MD
Outcome results
None listed