Dual Target CAR-T Cells in B-cell Acute Lymphoblastic Leukemia

Prospectively evaluate the safety and effectiveness of CD19/CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia. Strictly follow the inclusion criteria to screen eligible subjects for inclusion in clinical trials. The selected patients received CD19/CD22 dual-target CAR-T cell therapy. After the treatment is over, follow-up regularly to determine the survival status and follow-up treatment.

• Dual target CAR-T cell therapy (Biological): CD19/CD22 dual target CAR-T cell therapy

Primary outcomes

• Complete remission rate [From date of initial treatment to the end of follow up, up to 2 years]: 1. No blasts in peripheral blood, no extramedullary leukemia; 2. Three-line bone marrow hematopoietic recovery, primitive cells <5%; 3. Peripheral blood absolute neutrophil count>1.0×10\^9/L; 4. Peripheral blood platelet count>100×10\^9/L; 5. No recurrence within 4 weeks

Secondary outcomes

• Overall survival rate [From admission to the end of follow up, up to 2 years.]: The proportion of surviving patients at the end of the study.

Sex: All, ages: 14 Years to 75 Years

Inclusion Criteria:

* Subjects must meet the following criteria to participate in this study:

  1. 14-75 years old, no gender limit;
  2. According to the 2020 World Health Organization (WHO) diagnostic criteria, it is diagnosed as relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL);
  3. ECOG behavior status score is 0-2 points;
  4. Expected survival time ≥ 3 months;
  5. No contraindications to peripheral apheresis;
  6. Flow cytometry confirms that the original cells express CD22;
  7. Those who are tolerant to CD19 CAR-T cell therapy or those with low CD19 expression;
  8. No serious heart, lung, liver or kidney disease;
  9. Ability to understand and willing to sign the informed consent form for this trial.

Exclusion Criteria:

* Patients with any of the following cannot be included in this study:

  1. The original cells expressing CD19 and CD22 are negative;
  2. There is active infection;
  3. Abnormal liver function ( glutamic-pyruvic transaminase>1.5×ULN, glutamic oxalacetic transaminase>2.5×ULN), abnormal renal function (serum creatinine>1.5×ULN);
  4. People with unstable angina or New York Heart Association class 3/4 congestive heart failure, multiple organ dysfunction;
  5. HIV/AIDS patients;
  6. Those who need long-term anticoagulation (warfarin or heparin), antiplatelet (aspirin, dose>300mg/d; clopidogrel, dose>75mg/d) treatment;
  7. Those who received radiotherapy within 4 weeks before the start of the study (blood sampling);
  8. Known or suspected drug abuse or alcohol dependence;
  9. People with mental illness or other conditions cannot obtain informed consent, and cannot cooperate with the requirements for completing the experimental treatment and inspection procedures;
  10. Those who have participated in other clinical trials within 30 days;
  11. Pregnant or lactating women, male subjects (or their partners) or female subjects have a pregnancy plan during the study period to 6 months after the end of the test, and are unwilling to use a medically approved effective contraceptive measure during the test period (Such as intrauterine device or condom);
  12. The investigator judged that it is not suitable to participate in this trial.

• Li Yu, Dr, Principal investigator, Shenzhen University General Hospital