relapsed or refractory acute myeloid leukemia(r/r AML)
Conditions
Interventions
dose escalation group:CAR-T
dose expansion group:CAR-T
Sponsors
The First Affiliated Hospital of Medical College of Zhejiang University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the informed consent and expect to complete the follow-up examination and treatment of the study procedure. 2. Aged range from 18 to 70 years (including the threshold value), gender is not limited. 3. In accordance with the diagnosis of AML classified by WHO in 2016 and the diagnostic criteria of relapsed and refractory AML in Chinese Guidelines for Diagnosis and Treatment of Relapsed and Refractory acute myeloid Leukemia (2017 Edition), there is currently no suitable situation for clinically relevant treatment and registered clinical trials: (1) Diagnostic criteria for recurrent AML: recurrence of leukemia cells in peripheral blood after complete response (CR) or original cells in bone marrow >0.050 (except for other causes such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; (2) Diagnostic criteria for refractory AML: initial patients who failed to respond to 2 courses of treatment with standard protocols; Patients with CR relapse within 12 months after consolidation and intensive treatment; Patients who relapsed after 12 months but failed conventional chemotherapy; Patients with two or more relapses; Extramedullary leukemia persists. 4. AML Blast flow confirmed positive expression of CLL1. 5. The patient has recovered from toxicity from prior treatment, i.e., CTCAE toxicity grade =60 mL/min; (5) Hemoglobin >=60g/L or maintain the hemoglobin level after transfusion; (6) Indoor oxygen saturation >=92%; (7) Left ventricular ejection fraction (LVEF) >=45%. 8. Female patients shall also meet the following criteria to be considered for inclusion: (1) Sterile, defined as: 1) Had undergone hysterectomy or bilateral oophorectomy; 2) Had received bilateral tubal ligation; 3) Menopause (complete menopause >= 1 year); (2) Be fertile, but have a negative serum pregnancy test at screening, and agree to use a medically approved contraceptive method (e.g., IUD, contraceptive, or condom) before and during study enrollment until 1 year after the last study medication. 9. Sexually active male patients must consent to barrier contraception or complete abstinence.
Exclusion criteria
Exclusion criteria: 1. Acute promyelocytic leukemia was diagnosed. 2. Evidence of central nervous system invasion or craniocerebral neuropathy. 3. Hepatitis B surface antigen (HBsAg) positive, Hepatitis B core antibody (HBcAb) positive; Hepatitis C virus (HCV) antibody positive; Human immunodeficiency virus (HIV) antibody positive; Cytomegalovirus (CMV) DNA test positive; Syphilis antibody positive. 4. Patients with a history of severe allergy [A history of severe allergy is defined as secondary or above allergic reaction, which occurs when any of the following clinical manifestations occur: Airway obstruction (runny nose, cough, wheezing, dyspnea), tachycardia, hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), urinary and urinary incontinence, laryngeal edema, bronchospasm, cyanosis, shock, respiratory, cardiac arrest] or are known to be allergic to any drug active ingredient, excipients or mouse derived products or xenoproteins contained in this test (including the eluent regimen). 5. Severe heart disease, including but not limited to severe arrhythmia, unstable angina, massive myocardial infarction, New York Heart Association class ? or ? cardiac insufficiency, refractory hypertension (refractory hypertension is defined as: On the basis of improving life style, patients with reasonable and tolerable sufficient amount of >=3 antihypertensive drugs (including diuretics) for > 1 month whose blood pressure is still not up to the standard or who take >=4 antihypertensive drugs can effectively control blood pressure). 6. Patients who have previously received organ transplantation or are preparing to receive organ transplantation (except hematopoietic stem cell transplantation). 7. Patients with acute and chronic graft versus host disease (GVHD). 8. Patients who received hematopoietic stem cell transplantation within 6 weeks before screening. 9. Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES)). 10. Patients with acute tumor symptoms (such as spinal cord compression, intestinal obstruction, leukocytostasis, tumolysis syndrome, etc.) prior to screening or transfusion require emergency treatment. 11. There are uncontrolled bacterial, fungal, viral or other infections that require antibiotic treatment. 12. Patients who had received major surgical operations (excluding diagnostic operations and biopsies) within 4 weeks prior to drenching or planned to undergo major surgical operations during the study period, or whose surgical wounds had not fully healed before enrollment. 13. Patients with serious mental illness. 14. Hematopoietic cytokine drugs such as erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) that have an effect on patients' blood image were transfused or administered within 2 weeks before the scheduled collection of peripheral blood mononuclear cells (PBMC), and the researchers judged that it had an effect on cell preparation. 15. At the time of screening, hormonal or immunosuppressive drugs were being received within 2 weeks of the planned PBMC collection and were judged by the investigator to have an effect on cell preparation. (1) Hormones: Patients who were receiving systemic steroid therapy within 2 weeks of the sch
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| dose limited toxicity, DLT;maximal tolerable dose, MTD;safety index; | — |
Secondary
| Measure | Time frame |
|---|---|
| CAR-T in peripheral blood;complete response rate, CRR;partial remission rate, PRR;overall response rate, ORR;duration of remission, DOR;relapse-free survival, RFS;event free survival, EFS;overall survival, OS;MRD negative rate;median bone marrow protocell decline;proportion of subjects weaning from transfusion;anti-drug antibodies, ADA;cytokine;proportion of CLL1-positive tumor cells; | — |
Countries
China
Contacts
Public ContactJin Jie
Outcome results
None listed