NCT03778346

Brief Summary

According to the high expression of tumor cell-associated antigen CD138, integrin β7, CS1, CD38 and BCMA in patients with refractory/recurrent multiple myeloma, the fourth generation of CAR-T cells(simultaneously expressing IL7 and CCL19) with 10 different dual target combinations are used to minimize the tumor burden in the patient individually and precisely and improve the immunosuppressive microenvironment of the tumor , thereby effectively treating refractory/recurrent multiple myeloma .

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2018

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 15, 2018

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

December 14, 2018

Completed
5 days until next milestone

First Posted

Study publicly available on registry

December 19, 2018

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

November 18, 2020

Status Verified

November 1, 2020

Enrollment Period

3.6 years

First QC Date

December 14, 2018

Last Update Submit

November 16, 2020

Conditions

RRMM

Outcome Measures

Primary Outcomes (1)

  • Adverse events that are related to treatment

    Safety and tolerability measured by occurrence of study related adverse effects defined by NCI-CTCAE v4.03

    2 years

Secondary Outcomes (2)

  • 2 year overall survival(OS)

    2 yaers

  • 3 year progression free survival (PFS)

    3 yaers

Study Arms (1)

CAR-T therapy in multiple myeloma

EXPERIMENTAL

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.

Biological: CAR-T therapy in Relapsed/Refractory multiple myeloma

Interventions

CAR-T therapy in Relapsed/Refractory multiple myelomaBIOLOGICAL

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

CAR-T therapy in multiple myeloma

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients who meet the requirements voluntarily participate in the study and sign the Informed Consent Form.
  • Age is 18 to 80 years old, gender is not limited.
  • 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.
  • The Eastern Cancer Cooperative Group (ECOG) scores 0 to 2 (the tumor causes bone pain).
  • The expected survival period is more than 12 weeks.
  • No other malignant tumors, severe autoimmune diseases or congenital immunodeficiency, serious progressive infection, cranial nerve disorder or mental illness.

You may not qualify if:

  • Pregnant or lactating women.
  • Patients with uncontrollable active infections.
  • Patients with systemic steroids; recent or current use of inhaled steroids is not excluded.
  • Previously involved CAR-T cell therapies produced any uncontrolled disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Jinhong Jiang

Lishui, Zhejiang, 323000, China

RECRUITING

The Sixth Affiliated Hospital of Wenzhou Medical University

Lishui, Zhejiang, 323000, China

RECRUITING

Zhejiang QiXin Biotech

Wenzhou, Zhejiang, 325035, China

RECRUITING

Related Publications (11)

  • 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.

    PMID: 27571406BACKGROUND

  • 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.

    PMID: 29505028BACKGROUND

  • 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.

    PMID: 29515236BACKGROUND

  • 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.

    PMID: 28187291BACKGROUND

  • 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.

    PMID: 29106400BACKGROUND

  • 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.

    PMID: 26858358BACKGROUND

  • 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.

    PMID: 29812997BACKGROUND

  • 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.

    PMID: 29899820BACKGROUND

  • 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.

    PMID: 28928126BACKGROUND

  • 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.

    PMID: 25985798BACKGROUND

  • 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.

    PMID: 33767695DERIVED

MeSH Terms

Interventions

Immunotherapy, Adoptive

Intervention Hierarchy (Ancestors)

Adoptive TransferImmunization, PassiveImmunizationImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative Techniques

Study Officials

  • Bingmu Fang, M.D

    Lishui Country People's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Bingmu Fang, M.D

CONTACT

0578-2780108fbm636@163.com

Yonghua Liu, M.D

CONTACT

liuyonghua2010@163.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 14, 2018

First Posted

December 19, 2018

Study Start

November 15, 2018

Primary Completion

June 30, 2022

Study Completion

December 31, 2022

Last Updated

November 18, 2020

Record last verified: 2020-11

Locations

CN(3)