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A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Primary Purpose

Scleroderma, Autoimmune Diseases

Status

Recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Assigned Interventions CD19/BCMA CAR T-cells

About this trial

This is an interventional treatment trial for Scleroderma focused on measuring Scleroderma, CD19 CAR T-cell therapy, BCMA CAR T-cell therapy

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Scleroderma with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment
Estimated survival time> 12 weeks;
Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up;
Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

Subjects with any of the following exclusion criteria were not eligible for this trial:
1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
7. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
8. Other uncontrolled diseases that were not suitable for this trial;
9. Patients with HIV infection;
10. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study
11. Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L
12. Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.

Sites / Locations

The First Affiliated Hospital, College of Medicine, Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment of Scleroderma

Arm Description

Experimental：Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject.

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (DLT)

Adverse events assessed according to NCI-CTCAE v5.0 criteria

Incidence of treatment-emergent adverse events (TEAEs)

Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

Concentration of CAR-T cells

In peripheral blood

Objective Response Rate, ORR

Proportion of subjects with complete or partial remission

Disease control rate, DCR

The percentage of patients with remission and stable disease after treatment in the total evaluable cases.

Duration of remission, DOR

The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause

Progression-free survival, PFS

The time from cell reinfusion to the first assessment of disease progression or death from any cause

Overall survival, OS

The time from the cell reinfusion to death due to any cause

Full Information

NCT ID

NCT05085444

First Posted

October 11, 2021

Last Updated

October 11, 2021

Sponsor

Zhejiang University

Collaborators

Yake Biotechnology Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT05085444

Brief Title

A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Official Title

A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Recruiting

Study Start Date

October 8, 2021 (Actual)

Primary Completion Date

October 8, 2024 (Anticipated)

Study Completion Date

October 8, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Zhejiang University

Collaborators

Yake Biotechnology Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

Detailed Description

Autoimmune diseases only show local pathological damage, but more often systemic lesions. If not diagnosed and treated in time or poorly controlled, a risk of disability or even death as the course of the disease progresses. Studies have shown that B cells can present their own antigens to autoimmune T cells to promote the release of inflammatory factors, or they can differentiate into plasma cells to release autoantibodies, and play an important role in the occurrence and progression of autoimmune diseases. In recent years, it has become a major research focus to deplete B cells in patients or inhibit B cell function. This research focuses on CAR-T cells killing B cells. This fully reflects the application prospects of CAR-T cells in autoimmune diseases. Based on the current research progress, our center intends to conduct research on the safety and effectiveness of CD19/BCMA CAR-T cells in the treatment of refractory scleroderma

6. Conditions and Keywords

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

Scleroderma, Autoimmune Diseases

Keywords

Scleroderma, CD19 CAR T-cell therapy, BCMA CAR T-cell therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment of Scleroderma

Arm Type

Experimental

Arm Description

Experimental：Administration of CD19/BCMA CAR T-cells A dose levels of 1-4*10E6/kg are administrated for each subject.

Intervention Type

Biological

Intervention Name(s)

Assigned Interventions CD19/BCMA CAR T-cells

Intervention Description

Drug: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Name: CD19/BCMA CAR T-cells injection

Primary Outcome Measure Information:

Title

Dose-limiting toxicity (DLT)

Description

Adverse events assessed according to NCI-CTCAE v5.0 criteria

Time Frame

Baseline up to 28 days after CD19/BCMA CAR T-cells infusion

Title

Incidence of treatment-emergent adverse events (TEAEs)

Description

Incidence of treatment-emergent adverse events [Safety and Tolerability]

Time Frame

Up to 90 days after CD19/BCMA CAR T-cells infusion

Secondary Outcome Measure Information:

Title

Concentration of CAR-T cells

Description

In peripheral blood

Time Frame

From admission to the end of the follow-up, up to 2 years

Title

Objective Response Rate, ORR

Description

Proportion of subjects with complete or partial remission

Time Frame

In 3 months of CD19/BCMA CAR-T cell infusion

Title

Disease control rate, DCR

Description

The percentage of patients with remission and stable disease after treatment in the total evaluable cases.

Time Frame

From Day 28 CD19/BCMA CAR-T infusion up to 2 years

Title

Duration of remission, DOR

Description

The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause

Time Frame

24 months post CD19/BCMA CAR-T cells infusion

Title

Progression-free survival, PFS

Description

The time from cell reinfusion to the first assessment of disease progression or death from any cause

Time Frame

24 months post CD19/BCMA CAR-Tcells infusion

Title

Overall survival, OS

Description

The time from the cell reinfusion to death due to any cause

Time Frame

From CD19/BCMA CAR-T infusion to death，up to 2 years

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Scleroderma with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment Estimated survival time> 12 weeks; Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: Subjects with any of the following exclusion criteria were not eligible for this trial: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; Other uncontrolled diseases that were not suitable for this trial; Patients with HIV infection; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study Platelets ≥30×10E9/L, and absolute lymphocyte count ≥1.0×10E9/L Methylprednisolone (maximum dose 1mg/kg) or prednisone (maximum dose 1.25mg/kg) instead of immunosuppressive agents to control the disease.

Central Contact Person:

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

He Huang, PhD

Phone

86-13605714822

hehuangyu@126.com

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

Yongxian Hu, PhD

Phone

86-15957162012

huyongxian2000@aliyun.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

He Huang, PhD

Organizational Affiliation

First Affiliated Hospital of Zhejiang University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The First Affiliated Hospital, College of Medicine, Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310003

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

He Huang, PhD

Phone

86-13605714822

hehuangyu@126.com

First Name & Middle Initial & Last Name & Degree

Yongxian Hu, PhD

Phone

86-15957162012

huyongxian2000@aliyun.com

12. IPD Sharing Statement

Learn more about this trial

A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma

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