A Study of CD19 Redirected Autologous T Cells for CD19 Positive Systemic Lupus Erythematosus (SLE)

February 4, 2017 updated by: Shanghai GeneChem Co., Ltd.

An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)

CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of the central nervous system). SLE is a kind of autoimmune diseases which involving multiple systems, organs and with the present of a variety of autoantibodies. In the conventional treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells in the treatment of SLE.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.

Study Type

Interventional

Enrollment (Anticipated)

5

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 Locations

  • China
      • Shanghai, China, 200127
        • Recruiting
        • Shanghai Jiaotong University School of Medicine, Renji Hospital
        • Contact:

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

14 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical diagnosis of systemic lupus erythematosus (SLE) patients
  • Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry
  • Age: 18-69 years old
  • Creatinine < 1.5 mg/dl
  • cardiac ejection fraction>55%
  • hemoglobin>9g/dL
  • Bilirubin <2.0 mg/dl
  • Successful test expansion of T-cells
  • Adequate venous access for apheresis, and no other contraindications for leukapheresis
  • Voluntary informed consent is given

Exclusion Criteria:

  • Pregnant or lactating women
  • Uncontrolled active infection
  • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
  • Previously treatment with any gene therapy products
  • Feasibility assessment during screening demonstrates<5% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
  • Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, serious arrhythmia)

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reduce B cells
Patients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity.
Drug: cyclophosphamide
Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.
Other Names:
  • Cy
Experimental: Treatment of SLE
Patients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE.
Drug: anti-CD19-CAR-T cells
A 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge & transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min.
Other Names:
  • 2nd CAR-T

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of CAR-T cell（i.v.）by number of patients with adverse event
Time Frame: 6 weeks
adverse event is evaluated with CTCAE, version 4.0
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with tumor response
Time Frame: 8 weeks
summarize tumor response by overall response rates
8 weeks
3. Detection of transferred T cells in the circulation using quantitative -PCR
Time Frame: 6 weeks
6 weeks

Collaborators and Investigators

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

Sponsor

Shanghai GeneChem Co., Ltd.

Collaborators

RenJi Hospital

Investigators

  • Principal Investigator: Qiang Guo, Doctor, RenJi Hospital

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 (Anticipated)

March 1, 2017

Primary Completion (Anticipated)

January 1, 2018

Study Completion (Anticipated)

March 1, 2018

Study Registration Dates

First Submitted

January 22, 2017

First Submitted That Met QC Criteria

January 22, 2017

First Posted (Estimate)

January 25, 2017

Study Record Updates

Last Update Posted (Estimate)

February 7, 2017

Last Update Submitted That Met QC Criteria

February 4, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CD19-CART for SLE

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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