A Clinical Study on the Safety and Effectiveness of donor derived CD19 CAR-T Cells in the treatment of R/R B-cell acute lymphoblastic leukemia

In this study, 15 patients with relapsed refractory B-cell acute lymphoblastic leukemia were proposed to undergo CD19 CAR-T Cells therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of CD19 CAR-T Cells therapy for relapsed refractory B-cell acute lymphoblastic leukemia; At the same time, on the basis of expanding the sample size, more safety data on CD19 CAR-T Cells treatment for relapsed refractory B-cell acute lymphoblastic leukemia were accumulated.

Inclusion Criteria:

• 1. Age ≥18 years old, gender unlimited;

• 2. Abnormal B cell immunotyping was CD19 positive;

• 3. Patients diagnosed with B-cell acute lymphoblastic leukemia by histological or immunotyping;

• 4. Meets the diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and includes any of the following conditions:

  1. No CR was obtained after standard chemotherapy;
  2. CR was induced for the first time, but the duration of CR was less than 12 months;
  3. R/R B-ALL that does not work after the first or more remedial treatments;
  4. Two or more relapses;

• 5. The researchers believed that the patient had been adequately treated, such as auto-HSCT, auto-CART could not be prepared or preparation failed. Autologous CAR-T preparation failure was defined as including too few autologous lymphocytes (<1×109) or insufficient expansion during preparation or failure to meet the release criteria;

• 6. Total bilirubin ≤51 ( μmol/L), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal, creatinine ≤176.8 (μmol/L);

• 7. Absolute neutrophil count: ≥ 0.5×109/L; Platelet: ≥ 30×109/L; Hemoglobin ≧60g/L;

• 8. Echocardiography showed left ventricular ejection fraction (LVEF) ≥40%;

• 9. The estimated survival is more than 3 months;

• 10. ECOG score 0-2;

• 11. Women and men who are fertile must consent to the use of appropriate contraception before entering the study, during study participation, and for 6 months after transfusion (the safety of this therapy for the unborn child is not known, with unknown risks);

• 12. Subjects who are willing to participate in the study are able to understand and have the ability to sign informed consent.

Exclusion Criteria:

• 1. Known allergies to research preconditioning measures, etc;
• 2. People with a history of epilepsy or other central nervous system disorders;
• 3. People with a history of prolonged QT or severe heart disease;
• 4. Less than 100 days after receiving allogeneic hematopoietic stem cell transplantation;
• 5. Hiv-infected person;
• 6. Persons with active hepatitis B or C virus; Those who are not cured have active infections;
• 7. Insufficient amplification ability (< 5x) in response to CD3 / CD28 costimulatory signals;
• 8. Combined use of systemic steroids (e.g., prednisone ≥20mg) within 3 days prior to screening, except for ongoing or intermittent use of topical, inhaled or intranasal steroids within 2 weeks or at present; Or have systemic diseases that require long-term use of immunological agents;
• 9. Patients who received anti-cancer chemotherapy or other drugs within 2 weeks prior to screening;
• 10. Any situation that the investigator believes may increase the risk of the subjects or interfere with the study results.