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| Name | Class |
|---|---|
| Xuzhou Medical University | OTHER |
| Shanghai Jiao Tong University School of Medicine | OTHER |
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Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.
To determine:
Primary Outcome Measure:
The Overall complete remission rate and one-year survival rate of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is superior to or at least not worse than two kinds of single target treatments in the treatment of CD19+/CD20+ B-cell lymphomas.
The risk of cancer recurrence in a year of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is inferior to two kinds of single target treatments.
Secondary Outcome Measures:
Evaluate the initial effect time, time to disease progression, and life quality improvement of combination transfer compare to single target treatments.
Evaluate the safety and tolerability of combination transfer compare to single target treatments by observation of high fever duration in patients and testing related cell factor level in peripheral blood.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mixed CD19/CD20 CAR-T Transfer | Experimental | Subjects with CD19+/CD20+ B-cell lymphomas will be infused with CD19-targeting CAR T Cells and CD20-targeting CAR T Cells in one time or in parts |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mixed CD19/CD20 CAR-T Transfer | Biological | Autologous CD19 CAR-T cells and CD20 CAR-T cells with average 1-5*10^6 cells/kg body weight,separately. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall complete remission rate | The complete remission rate will be evaluated by routine methods. | Half a year |
| Measure | Description | Time Frame |
|---|---|---|
| The initial effect time | The initial effect time will be recorded. | 1 year |
| The one-year survival rate | The one-year survival rate will be recorded. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xin Wang, M.D. | Contact | 185-1602-2625 | +86 | wangxin928@163.com |
| Jiang Cao, Ph.D. | Contact | 159-5146-8263 | +86 | zimu05067@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Shengqin Ye, M.D. | Shanghai Longyao Biotechnology Inc., Ltd. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Longyao Biotechnology Inc., Ltd. | Recruiting | Shanghai | Jingan | 200072 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25444722 | Background | Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ, Chen MX, Feng KC, Wang QS, Fu XB, Han WD. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16. | |
| 25572478 |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| 1 year |
| The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity) | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | 1 month |
| The time to disease progression | The time to disease progression will be counted after complete remission. | 1 year |
| The one-year recurrence | The one-year recurrence will be counted after complete remission. | 1 year |
| The life quality improvement | The life quality improvement will be evaluated by appetite,sleep,pain and mental state. | 1 year |
| Background |
| Witkowska M, Smolewski P. Emerging immunotherapy and strategies directly targeting B cells for the treatment of diffuse large B-cell lymphoma. Immunotherapy. 2015;7(1):37-46. doi: 10.2217/imt.14.93. |
| 26811520 | Background | Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, Gea-Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, Feldman SA, Iwamoto AT, Kurlander R, Maric I, Goy A, Hansen BG, Wilder JS, Blacklock-Schuver B, Hakim FT, Rosenberg SA, Gress RE, Kochenderfer JN. Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. J Clin Oncol. 2016 Apr 1;34(10):1112-21. doi: 10.1200/JCO.2015.64.5929. Epub 2016 Jan 25. |
| 28110394 | Background | Hay KA, Turtle CJ. Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. Drugs. 2017 Mar;77(3):237-245. doi: 10.1007/s40265-017-0690-8. |
| 34515338 | Derived | Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2. |
| 32608579 | Derived | Sang W, Shi M, Yang J, Cao J, Xu L, Yan D, Yao M, Liu H, Li W, Zhang B, Sun K, Song X, Sun C, Jiao J, Qin Y, Sang T, Ma Y, Wu M, Gao X, Cheng H, Yan Z, Li D, Sun H, Zhu F, Wang Y, Zeng L, Li Z, Zheng J, Xu K. Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. Cancer Med. 2020 Aug;9(16):5827-5838. doi: 10.1002/cam4.3259. Epub 2020 Jul 1. |