Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells
NCT ID: NCT03778346
Last Updated: 2020-11-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1
30 participants
INTERVENTIONAL
2018-11-15
2022-12-31
Brief Summary
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Detailed Description
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MM is genetically and phenotypically heterogeneous,Antigen escape and relapse after CAR-T treatment is a global problem， so the effective treatment of refractory/relapsing multiple myeloma with CAR-T cells usually requires targeting multiple antigens. The investigators use Integrin β7(a large family of molecules that are central regulators in multicellular biology and orchestrating cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function), BCMA(highly expressed on malignant MM plasma cells and providing a substantial antiapoptotic signal making it an encouraging target for BCMA-directed immunotherapy),CS1(encoded by the SLAMF7 gene,a robust marker of normal plasma cells and malignant plasma),CD38(encoded by the CD38 gene and functioning in cell adhesion, signal transduction and calcium signaling) and CD138(known as syndecan 1, a surface protein expressed on most healthy and malignant plasma cells as an adhesion protein, binding collagen and fibronectin molecules located in the extracellular matrix. ) as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells ,thereby effectively treating refractory/recurrent multiple myeloma .
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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CAR-T therapy in multiple myeloma
In order to assess the safety and validity of using the Fourth Genenation of CAR-T therapy refractory/rela-psed multiple myeloma patients with one kind of BCMA-CART,CD138-CART,CD38-CART , Integrin β7-CART or 10 different combinations ,subjects will receive 10\^6-10\^7/Kg transduced CAR-T cells at one time.
CAR-T therapy in Relapsed/Refractory multiple myeloma
Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells to treat Relapsed/Refractory multiple myeloma
Interventions
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CAR-T therapy in Relapsed/Refractory multiple myeloma
Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells to treat Relapsed/Refractory multiple myeloma
Eligibility Criteria
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Inclusion Criteria
2. Age is 18 to 80 years old, gender is not limited.
3. Patients with relapsed or refractory myeloma who meet the following criteria for multiple myeloma diagnostic criteria defined by the IMWG (2017): Subjects have received adequate prior treatment of at least 2 regimens; during the most recent treatment or after treatment , the disease progresses or recurs.
4. The Eastern Cancer Cooperative Group (ECOG) scores 0 to 2 (the tumor causes bone pain).
5. The expected survival period is more than 12 weeks.
6. No other malignant tumors, severe autoimmune diseases or congenital immunodeficiency, serious progressive infection, cranial nerve disorder or mental illness.
Exclusion Criteria
2. Patients with uncontrollable active infections.
3. Patients with systemic steroids; recent or current use of inhaled steroids is not excluded.
4. Previously involved CAR-T cell therapies produced any uncontrolled disease.
18 Years
80 Years
ALL
No
Sponsors
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Zhejiang Qixin Biotech
UNKNOWN
The Sixth Affiliated Hospital of Wenzhou Medical University
OTHER
Responsible Party
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Principal Investigators
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Bingmu Fang, M.D
Role: PRINCIPAL_INVESTIGATOR
Lishui Country People's Hospital
Locations
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Jinhong Jiang
Lishui, Zhejiang, China
The Sixth Affiliated Hospital of Wenzhou Medical University
Lishui, Zhejiang, China
Zhejiang QiXin Biotech
Wenzhou, Zhejiang, China
Countries
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Central Contacts
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Facility Contacts
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Jiang Jinhong, M.D
Role: primary
Jiang Jinhong, M.D
Role: backup
Bingmu Fang, M.D
Role: primary
M.D
Role: backup
Jimin Gao, M.D., Ph.D.
Role: primary
Ai Zhao, M.D., Ph.D.
Role: backup
References
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Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, Scholler J, Lacey SF, Melenhorst JJ, Morrissette JJ, Christian DA, Hunter CA, Kalos M, Porter DL, June CH, Grupp SA, Gill S. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016 Oct 3;126(10):3814-3826. doi: 10.1172/JCI87366. Epub 2016 Aug 29.
Adachi K, Kano Y, Nagai T, Okuyama N, Sakoda Y, Tamada K. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018 Apr;36(4):346-351. doi: 10.1038/nbt.4086. Epub 2018 Mar 5.
Petrov JC, Wada M, Pinz KG, Yan LE, Chen KH, Shuai X, Liu H, Chen X, Leung LH, Salman H, Hagag N, Liu F, Jiang X, Ma Y. Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. Leukemia. 2018 Jun;32(6):1317-1326. doi: 10.1038/s41375-018-0075-3. Epub 2018 Feb 25.
Lim WA, June CH. The Principles of Engineering Immune Cells to Treat Cancer. Cell. 2017 Feb 9;168(4):724-740. doi: 10.1016/j.cell.2017.01.016.
Hosen N, Matsunaga Y, Hasegawa K, Matsuno H, Nakamura Y, Makita M, Watanabe K, Yoshida M, Satoh K, Morimoto S, Fujiki F, Nakajima H, Nakata J, Nishida S, Tsuboi A, Oka Y, Manabe M, Ichihara H, Aoyama Y, Mugitani A, Nakao T, Hino M, Uchibori R, Ozawa K, Baba Y, Terakura S, Wada N, Morii E, Nishimura J, Takeda K, Oji Y, Sugiyama H, Takagi J, Kumanogoh A. The activated conformation of integrin beta7 is a novel multiple myeloma-specific target for CAR T cell therapy. Nat Med. 2017 Dec;23(12):1436-1443. doi: 10.1038/nm.4431. Epub 2017 Nov 6.
Drent E, Groen RW, Noort WA, Themeli M, Lammerts van Bueren JJ, Parren PW, Kuball J, Sebestyen Z, Yuan H, de Bruijn J, van de Donk NW, Martens AC, Lokhorst HM, Mutis T. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica. 2016 May;101(5):616-25. doi: 10.3324/haematol.2015.137620. Epub 2016 Feb 8.
Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, Stetler-Stevenson M, Salem D, Yuan C, Pavletic S, Kanakry JA, Ali SA, Mikkilineni L, Feldman SA, Stroncek DF, Hansen BG, Lawrence J, Patel R, Hakim F, Gress RE, Kochenderfer JN. T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. J Clin Oncol. 2018 Aug 1;36(22):2267-2280. doi: 10.1200/JCO.2018.77.8084. Epub 2018 May 29.
Bu DX, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG, Bennett P, Barton N, Wu Q, Zhang J, Wang Y, Wei L, Cogan S, Ezell T, Joshi S, Latimer KJ, Granda B, Tschantz WR, Young RM, Huet HA, Richardson CJ, Milone MC. Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget. 2018 May 25;9(40):25764-25780. doi: 10.18632/oncotarget.25359. eCollection 2018 May 25.
Mikkilineni L, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood. 2017 Dec 14;130(24):2594-2602. doi: 10.1182/blood-2017-06-793869. Epub 2017 Sep 19.
Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145-54. doi: 10.1517/14712598.2015.1046430. Epub 2015 May 18.
Duan D, Wang K, Wei C, Feng D, Liu Y, He Q, Xu X, Wang C, Zhao S, Lv L, Long J, Lin D, Zhao A, Fang B, Jiang J, Tang S, Gao J. The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. Front Immunol. 2021 Mar 5;12:609421. doi: 10.3389/fimmu.2021.609421. eCollection 2021.
Other Identifiers
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SixthAHWenzhouMU
Identifier Type: -
Identifier Source: org_study_id