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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
Sponsored by
Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  1. Scleroderma with positive CD19/BCMA expression , and the conventional treatment is not effective and (or) no effective treatment
  2. Estimated survival time> 12 weeks;
  3. 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;
  4. 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

First Posted
October 11, 2021
Last Updated
October 11, 2021
Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.
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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
No
Studies a U.S. FDA-regulated Device Product
No
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
No
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
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongxian Hu, PhD
Phone
86-15957162012
Email
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
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name & Degree
Yongxian Hu, PhD
Phone
86-15957162012
Email
huyongxian2000@aliyun.com

12. IPD Sharing Statement

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

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