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

November 16, 2020 updated by: The Sixth Affiliated Hospital of Wenzhou Medical University
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 .

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Bingmu Fang, M.D
  • Phone Number: 0578-2780108
  • Email: fbm636@163.com

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Lishui, Zhejiang, China, 323000
        • Recruiting
        • The Sixth Affiliated Hospital of Wenzhou Medical University
        • Contact:
        • Principal Investigator:
          • Bingmu Fang, M.D
      • Lishui, Zhejiang, China, 323000
        • Recruiting
        • Jinhong Jiang
        • Contact:
        • Contact:
          • Jiang Jinhong, M.D
        • Sub-Investigator:
          • Jiang Jinhong
      • Wenzhou, Zhejiang, China, 325035
        • Recruiting
        • Zhejiang QiXin Biotech
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jimin Gao, M.D., Ph.D.
        • Sub-Investigator:
          • Ai Zhao, M.D., Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 yaers
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
3 yaers

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Sixth Affiliated Hospital of Wenzhou Medical University

Collaborators

Zhejiang Qixin Biotech

Investigators

  • Principal Investigator: Bingmu Fang, M.D, Lishui Country People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2018

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

December 14, 2018

First Submitted That Met QC Criteria

December 17, 2018

First Posted (Actual)

December 19, 2018

Study Record Updates

Last Update Posted (Actual)

November 18, 2020

Last Update Submitted That Met QC Criteria

November 16, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • SixthAHWenzhouMU

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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