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| Name | Class |
|---|---|
| Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | INDUSTRY |
| The Second People's Hospital of Huai'an | OTHER |
| Third Military Medical University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAR T-cell therapy | Experimental | Patients enrolled will receive infusion of CD19-targeting CART-cells |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAR T-cell therapy | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Depei Wu, M.D., Ph.D. | The First Affiliated Hospital of Soochow University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Fisrt Affiliated Hospital of Soochow University | Suzhou | Jiangsu | 215006 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24876563 | Background | 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. | |
| 37095120 | Derived | 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. |
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| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D016219 | Immunotherapy, Adoptive |
| ID | Term |
|---|---|
| D019264 | Adoptive Transfer |
| D007116 | Immunization, Passive |
| D007114 | Immunization |
| D007167 | Immunotherapy |
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|
| 3 year post infusion |
| 35013456 | Derived | 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. |
| 32399214 | Derived | 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. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D056747 |
| Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |