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Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03778346
Recruitment Status : Unknown
Verified November 2020 by The Sixth Affiliated Hospital of Wenzhou Medical University.
Recruitment status was:  Recruiting
First Posted : December 19, 2018
Last Update Posted : November 18, 2020
Sponsor:
Collaborator:
Zhejiang Qixin Biotech
Information provided by (Responsible Party):
The Sixth Affiliated Hospital of Wenzhou Medical University

Study Description
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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 .

Condition or disease Intervention/treatment Phase
RRMM Biological: CAR-T therapy in Relapsed/Refractory multiple myeloma Phase 1

Detailed Description:

Multiple myeloma（MM） is one of the most common malignant diseases in the blood system.There is still no cure for the disease which only control the development of the disease in various ways including proteasome inhibitors and immune regulator and hematopoietic stem cell transplantation . Combined with the advantages of multiple therapies, chimeric antigen receptor T cells (CAR-T) have gradually becoming one of the strongest and most powerful weapons against multiple myeloma.The basic principle is to use the patient's own immune cells to clear cancer cells.

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 .

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells
Actual Study Start Date : November 15, 2018
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Biological: 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


Outcome Measures
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Primary Outcome Measures :
  1. Adverse events that are related to treatment [ Time Frame: 2 years ]
    Safety and tolerability measured by occurrence of study related adverse effects defined by NCI-CTCAE v4.03


Secondary Outcome Measures :
  1. 2 year overall survival(OS) [ Time Frame: 2 yaers ]
    To estimate 2 year overall survival(OS) after BCMA/CD138/CD38/Integrinβ7/CS1-CART infusion and sequential treatment with Relapsed/Refractory MM

  2. 3 year progression free survival (PFS) [ Time Frame: 3 yaers ]
    To estimate 3 year progression free survival after BCMA/CD138/CD38/Integrinβ7/CS1 CART infusion and sequential treatment with Relapsed/Refractory MM


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who meet the requirements voluntarily participate in the study and sign the Informed Consent Form.
  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:

  1. Pregnant or lactating women.
  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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03778346


Contacts
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Contact: Bingmu Fang, M.D 0578-2780108 fbm636@163.com
Contact: Yonghua Liu, M.D liuyonghua2010@163.com

Locations
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China, Zhejiang
Jinhong Jiang Recruiting
Lishui, Zhejiang, China, 323000
Contact: Jiang Jinhong, M.D    0578-2780108    xyk1069@163.com   
Contact: Jiang Jinhong, M.D         
Sub-Investigator: Jiang Jinhong         
The Sixth Affiliated Hospital of Wenzhou Medical University Recruiting
Lishui, Zhejiang, China, 323000
Contact: Bingmu Fang, M.D    0578-2780108    fbm636@163.com   
Contact: M.D         
Principal Investigator: Bingmu Fang, M.D         
Zhejiang QiXin Biotech Recruiting
Wenzhou, Zhejiang, China, 325035
Contact: Jimin Gao, M.D., Ph.D.    86-577-86699341    jimingao@yahoo.com   
Contact: Ai Zhao, M.D., Ph.D.    86-577-86699341    zhaoai618@126.com   
Principal Investigator: Jimin Gao, M.D., Ph.D.         
Sub-Investigator: Ai Zhao, M.D., Ph.D.         
Sponsors and Collaborators
The Sixth Affiliated Hospital of Wenzhou Medical University
Zhejiang Qixin Biotech
Investigators
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Principal Investigator: Bingmu Fang, M.D Lishui Country People's Hospital
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: The Sixth Affiliated Hospital of Wenzhou Medical University
ClinicalTrials.gov Identifier: NCT03778346    
Other Study ID Numbers: SixthAHWenzhouMU
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: November 18, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No