Acute myeloid leukemia
Conditions
Interventions
Dose escalation:Chimeric Antigen Receptor T-Cell
Dose expansion:Chimeric Antigen Receptor T-Cell
Sponsors
Hebei Yanda Lu Daopei Hospital
Eligibility
Sex/Gender
All
Age
2 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the informed consent and be willing to complete the follow-up examination and treatment of the research procedures; 2. Age 2~60 years old, gender is not limited; 3. Meet the diagnosis of AML according to the 2016 WHO classification, and the diagnostic criteria for relapsed and refractory in the The Guidelines for Diagnosis and Treatment of Acute Myelogenous Leukemia (Relapse/Refractory) in China (2017), and there are currently no appropriate clinically relevant treatments and registered clinical trials: (1) Diagnostic criteria for relapsed AML: leukemia cells reappeared in peripheral blood after complete remission (CR) or blasts >0.050 in bone marrow (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; (2) Diagnostic criteria for refractory AML: naive patients who were ineffective after 2 courses of standard regimens, patients who relapsed within 12 months after consolidation and intensive therapy after CR, patients who relapsed after 12 months but were ineffective after conventional chemotherapy, 2 times or multiple recurrences, or persistent extramedullary leukemia. 4. The CLL1 positive expression rate of AML blasts is greater than 70%; 5. The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 2 (unless the abnormality is related to the tumor or is in a stable state as judged by the investigator, which has little effect on safety or efficacy); 6. ECOG performance status score of 0 to 2 and expected survival time greater than 3 months; 7. Has proper organ function: (1) Aspartate aminotransferase (AST) =60 mL/min; (5) Hemoglobin >= 60g/L or maintained at this level after blood transfusion; (6) Indoor oxygen saturation >=92%; (7) Left ventricular ejection fraction (LVEF) >=45%. 8. Female subjects must also meet the following criteria to be considered for inclusion: (1) No fertility, defined as: 1) Have had a hysterectomy or bilateral oophorectomy, or 2) Have had bilateral tubal ligation, or 3) Menopause (complete cessation of menstruation for >= 1 year); (2) Fertile, but have a negative serum pregnancy test at screening, and agree to take medically approved contraceptive measures (such as an intrauterine device, contraceptives, or condoms) before and during the study, until 1 year after the last study medication given. 9. Sexually active male patients must agree to barrier contraception or complete abstinence.
Exclusion criteria
Exclusion criteria: 1. Diagnosed as acute promyelocytic leukemia; 2. Have active central nervous system leukemia (in line with CNSL3 criteria) or craniocerebral space-occupying lesions determined by imaging examination; 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 Results >= 500 copies/mL; syphilis antibody positive; 4. Those with a history of severe allergies or known any of the active ingredients, excipients or mouse-derived products contained in the drug, or those allergic to xenogeneic proteins in this trial, including lymphocyte depletion regimens. Severe allergy history is defined as an allergic reaction of grade two or above, and any of the following clinical manifestations occur when an allergic reaction occurs: airway obstruction (runny nose, cough, wheezing, dyspnea), hypercardia tachycardia, hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), incontinence, laryngeal edema, bronchospasm, cyanosis, shock, respiration, cardiac arrest; 5. Severe heart disease, including but not limited to severe arrhythmia, unstable angina, massive myocardial infarction, New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory Hypertension is defined as: on the basis of improving lifestyle, a reasonable tolerable and sufficient amount of >=3 kinds of antihypertensive drugs (including diuretics) has been used for > 1 month and the blood pressure has not reached the standard, or the blood pressure can only be achieved effective control after taking >=4 kinds of antihypertensive drugs; 6. Those who have received organ transplants or are about to receive organ transplants (except for hematopoietic stem cell transplants); 7. Patients with acute and chronic graft-versus-host disease (GVHD); 8. Those who have received hematopoietic stem cell transplantation within 3 months before screening, and have active GVHD after discontinuation of immunosuppressive agents; 9. Active autoimmune or inflammatory diseases of the nervous system (eg, Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (eg, cerebral edema) , Posterior Reversible Encephalopathy Syndrome (PRES)); 10. Those who have tumor emergencies (such as spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome, etc.) before screening or reinfusion and need emergency treatment; 11. The presence of an uncontrolled bacterial, fungal, viral or other infection requiring antibiotic treatment; 12. Those who have undergone major surgical operations (except diagnostic surgery and biopsy) within 4 weeks before clearing the lymph cells, or those who plan to undergo major surgery during the study period, or those whose surgical wounds have not healed completely before enrollment; 13. Persons with severe mental illness; 14. Those who have received (attenuated) live virus vaccine within 4 weeks before screening; 15. Those who are alcoholics or have a history of drug abuse; 16. Patients with contraindications to any research procedure or with other medical conditions that may expose them to unacceptable risks at the discretion of the investigator and/or clinical criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| dose limited toxicity, DLT;Maximal Tolerable Dose, MTD;Safety index; | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete response rate, CRR;Partial remission rate, PRR;Overall response rate, ORR;Duration of remission, DOR;Relapse-Free Survival, RFS;Event free survival; | — |
Countries
China
Contacts
Public ContactPeihua Lu
Hebei Yanda Lu Daopei Hospital
Outcome results
None listed