Study Investigating the Safety of CD19 CAR-T Cells in Relapsed/Refractory AML Expressing CD19

Inclusion Criteria

• •Subject is ≥ 18 years of age at the time of signing the informed consent form,
• •Patient with AML that expresses CD19 by Flow-cytometry, (CD19 expression ≥ 70% of AML blasts)
• •Patients with R/R AML defined as:
• •* Primary refractory: absence of remission after two courses of induction chemotherapy,
• •* Secondary refractory: absence of remission after salvage treatment in relapsing patients,
• •* Post-transplant relapse in patients having had allo-HCT.
• •Lack of accessible targeted therapy that has not been previously utilized.
• •Eastern Cooperative Oncology Group (ECOG) performance status of \< 2,
• •Estimated life expectancy of \> 2 months,
• •Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) involvement,
• •Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia),
• •Platelet count ≥ 30000/uL,
• •Absolute lymphocyte count ≥ 200/uL,
• •Creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL/min,
• •Serum ALT/AST ≤ 2.5 upper limit of normal (ULN),
• •Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome,
• •Cardiac ejection fraction ≥ 45 %,
• •No clinically significant electrocardiogram (ECG) findings,
• •No clinically significant pleural effusion,
• •Baseline oxygen saturation \> 92 % on room air,
• •Female patients of childbearing potential must:
• •1. have a negative pregnancy test (blood) at screening visit.
• •2. either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the CAR-T cell infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal\] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled.
• •3. Agree to abstain from breast feeding during the study participation and for 1 year after the CAR-T cell infusion.
• •Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after the CAR-T cell infusion, even if he has undergone a successful vasectomy.