Clinical trial NCT03919240: CAR-T Cell Therapy Targeting to CD19 for R/R ALL
Official title: CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients with Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia with Failed Remission
Keywords: Acute Lymphoblastic Leukemia
Refractory and relapsed
Chimeric antigen receptor T-cell therapy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
name: The Second People's Hospital of Huai'an
name: Third Military Medical University
First posted: 2019-04-18
Enrollment: 196
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Completeremission
timeFrame: 1 month post infusion
measure: Minimal residual disease response
timeFrame: 1 month post infusion
measure: Leukemia-free survival
timeFrame: 3 year post infusion
Secondary outcomes:
measure: Overall survival
timeFrame: 3 year post infusion
measure: Cumulative incidence of relapse
timeFrame: 3 year post infusion
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The Fisrt Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee 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.
citation: Li 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.
citation: Liu 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.