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

Primary Purpose

Systemic Lupus Erythematosus (SLE)

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

cyclophosphamide

anti-CD19-CAR-T cells

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus (SLE) focused on measuring CD19, CAR-T, SLE

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Shanghai Jiaotong University School of Medicine, Renji HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Reduce B cells

Treatment of SLE

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety of CAR-T cell（i.v.）by number of patients with adverse event

adverse event is evaluated with CTCAE, version 4.0

Secondary Outcome Measures

Number of patients with tumor response

summarize tumor response by overall response rates

3. Detection of transferred T cells in the circulation using quantitative -PCR

Full Information

NCT ID

NCT03030976

First Posted

January 22, 2017

Last Updated

February 4, 2017

Sponsor

Shanghai GeneChem Co., Ltd.

Collaborators

RenJi Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03030976

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Unknown status

Study Start Date

March 2017 (Anticipated)

Primary Completion Date

January 2018 (Anticipated)

Study Completion Date

March 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai GeneChem Co., Ltd.

Collaborators

RenJi Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Lupus Erythematosus (SLE)

Keywords

CD19, CAR-T, SLE

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Reduce B cells

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment of SLE

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

Intervention Description

Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.

Intervention Type

Drug

Intervention Name(s)

anti-CD19-CAR-T cells

Other Intervention Name(s)

2nd CAR-T

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety of CAR-T cell（i.v.）by number of patients with adverse event

Description

adverse event is evaluated with CTCAE, version 4.0

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Number of patients with tumor response

Description

summarize tumor response by overall response rates

Time Frame

8 weeks

Title

3. Detection of transferred T cells in the circulation using quantitative -PCR

Time Frame

6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Qiang Guo, Doctor

Phone

86-21-63835620

bluedescent@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Xuejun Yu, Master

Phone

86-21-51320189

Ext

8306

yuxuejun@genechem.com.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Qiang Guo, Doctor

Organizational Affiliation

RenJi Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shanghai Jiaotong University School of Medicine, Renji Hospital

City

Shanghai

ZIP/Postal Code

200127

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qiang Guo, Doctor

Phone

86-21-63835620

bluedescent@126.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

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

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