cd19 hscar-t for refractory/relapsed cd19+ b-all patients

Conditions: Acute Lymphoblastic Leukemia

Summary: this phase ii study is to evaluate the efficacy and safety of a cd19-targeting humanized selective car-t (cd19 hscar-t) in refractory/relapsed cd19+ b-all leukemia patients who have no available curative treatment options, have a limited prognosis with currently available treatments, and were previously treated with a b cell directed cell therapy.

cd19+ b-all patients who have relapsed after murine-based cd19 car-t (cd19mcar-t) treatment and/or have limited clinical response to cd19mcar-t will be enrolled to receive cd19 hscar-t treatment.

Eligibility criteria:
inclusion criteria: 1. subjects with refractory/relapse b-cell all with no available curative treatment options (such as autologous or allogeneic sct); 2. subjects previously treated with b cell-directed engineered cell therapy are eligible if they meet the following criteria: 1. relapsed and/or mrd-positive after prior cell therapy; 2. partial response to prior cell therapy; 3. clinical and laboratory data are available; 3. documented cd19 expression after previous b cell-directed therapies; 4. aged 1 to 75 years; 5. kps\>40； 6. at least 2 weeks or 5 drug half-lives, whichever is shorter must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy; 7. women of childbearing potential must have a urine pregnancy test taken and proven negative prior to the treatment. all patients agree to use reliable methods of contraception during the trial period and throughout the last follow-up visit; 8. subjects with relapsed disease after prior allogeneic sct (myeloablative or non-myeloablative) will be eligible if the patients do not present with active gvhd and are not undergoing immunosuppressive regimes; 9. patients with cns3 (wcb ≥5/ml in csf with presence of lymphoblasts) disease will be eligible if the cns disease is responsive to therapy; 10. participation in the clinical trials should be voluntary with signed informed consent. exclusion criteria: 1. patients with hypervolemia (white blood cell count\> 50 x 10\^9 / l) or rapidly progressive disease that in the estimation of the investigators and sponsors would compromise the patient's ability to complete the study; 2. history of melanoma skin cancer or other primary tumors (eg, cervical cancer, bladder cancer, breast cancer) (except for those with 3 years or longer of cure); 3. patients with fungal, bacterial, viral, or other uncontrollable infections or infections requiring level 4 isolation (uti or inoculation assays may be performed if necessary); 4. patients with positive results for hiv, hbv, hcv tests; 5. with cns disorders such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with cns involvement; 6. history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac diseases within 12 months of enrollment, or with cardiac atrial or cardiac ventricular lymphoma; 7. patients that are receiving anticoagulant therapy or have ever coagulation disorders; 8. any medical condition that in the judgment of the sponsors/investigators is likely to interfere with assessment of safety or efficacy of study; 9. history of severe immediate hypersensitivity reaction to any of the agents used in this study; 10. female patients who are pregnant or breastfeeding; 11. feasibility assessment during screening demonstrates \<30% transduction of target lymphocytes, or insufficient expansion (\< 5-fold) in response to cd3/cd28 co-stimulation; 12. patients with any uncontrolled diseases that are unsuitable for enrollment; 13. cns3 disease that is progressive on therapy, or with cns parenchymal lesions that might increase the risk of cns toxicity; 14. any situation that is considered to potentially increase the risk of the subject or interfere with the outcome of the study; 15. patients who have been enrolled in other clinical studies.

Keywords: cd19 hscar-t b-all humanized selective car