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

CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients With Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Lymphoblastic Leukemia With Failed Remission
• Intervention / Treatment: Biological: CAR T-cell therapy

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The Fisrt Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAR T-cell therapy; Patients enrolled will receive infusion of CD19-targeting CART-cells

Biological: CAR T-cell therapy; All enrolled patients will initially enter Arm A and receive CD19-targeted CAR T-cell therapy at a target dose of 5~10×10E6 cells/kg after a lymphodepleting regimen consisting of fludarabine (30 mg/m²/day, days -5 to -3) and cyclophosphamide (300 mg/m²/day, days -5 to -3). Patients with an available eligible donor who consent to randomization will enter the RCT component and be randomized in a 2:1 ratio to Arm B1 (CAR T-cell therapy alone) or Arm B2 (CAR T-cell therapy followed by allo-HCT); all other patients will remain in Arm A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal residual disease response	defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection	1 month post infusion
Completeremission	defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery	1 month post infusion
Leukemia-free survival	calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up	3 year post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	calculating from the day of CAR T-cell infusion to death or the end of follow-up	3 year post infusion
Cumulative incidence of relapse	calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up	3 year post infusion

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Third Military Medical University; The Second People's Hospital of Huai'an; Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
• Investigators: Principal Investigator: Depei Wu, M.D., Ph.D., The First Affiliated Hospital of Soochow University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• Liu 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Acute Lymphoblastic Leukemia; Chimeric antigen receptor T-cell therapy; Refractory and relapsed
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunotherapy, Adoptive
• Other Study ID Numbers: SZ4601

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No