CAR-T Cell Therapy Targeting to CD19 for R/R ALL

Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct atrial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.

Sex

All

Inclusion Criteria:

* Diagnosed as CD19+ B-cell acute lymphoblastic leukemia;
* Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation;
* With an estimated survival of higher than 3 months (according to investigator's judgement);
* Sufficient organ function: left ventricular ejection fractions≥ 0.5 by echocardiography, creatinine \< 1.6 mg/dL, aspartate aminotransferase/aspartateaminotransferase \< 3 x upper limit of normal, bilirubin \<2.0 mg/dL;
* Karnofsky performance status ≥ 60 or ECOG ≤ 2.

Exclusion Criteria:

* Intolerant to immunosuppressive chemotherapies;
* With active infection or other uncontrolled complications;
* With history of seizure;
* Active hepatitis B or hepatitis C infection and HIV infection;
* Pregnant or lactating women, or patients refusing to take effective contraception measures;
* Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).

• BACKGROUNDLee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29. PMID 24876563
• DERIVEDLiu S, Zhang X, Dai H, Cui W, Yin J, Li Z, Yang X, Yang C, Xue S, Qiu H, Miao M, Chen S, Jin Z, Fu C, Li C, Sun A, Han Y, Wang Y, Yu L, Wu D, Cui Q, Tang X. Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy? Blood Cancer J. 2023 Apr 24;13(1):60. doi: 10.1038/s41408-023-00819-5. PMID 37095120
• DERIVEDLi M, Xue SL, Tang X, Xu J, Chen S, Han Y, Qiu H, Miao M, Xu N, Tan J, Kang L, Yu Z, Lou X, Xu Y, Chen J, Yan Z, Feng W, Wu D, Yu L. The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients. Sci Rep. 2022 Jan 10;12(1):378. doi: 10.1038/s41598-021-04296-3. PMID 35013456
• DERIVEDLiu ZF, Chen LY, Wang J, Kang LQ, Tang H, Zhou Y, Zhou HX, Sun AN, Wu DP, Xue SL. Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report. Biomark Res. 2020 May 6;8:12. doi: 10.1186/s40364-020-00193-5. eCollection 2020. PMID 32399214