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

Autoimmune Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05085444
• Other study ID #: CD19/BCMA-002
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 8, 2021
• Est. completion date: October 8, 2024

Study information

• Verified date: October 2021
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: October 8, 2024
• Est. primary completion date: October 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Localized
• Scleroderma, Systemic

Intervention

Biological:
• Assigned Interventions CD19/BCMA CAR T-cells
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

Locations

Country	Name	City	State
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Yake Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CD19/BCMA CAR T-cells infusion
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 90 days after CD19/BCMA CAR T-cells infusion
Secondary	Concentration of CAR-T cells	In peripheral blood	From admission to the end of the follow-up, up to 2 years
Secondary	Objective Response Rate, ORR	Proportion of subjects with complete or partial remission	In 3 months of CD19/BCMA CAR-T cell infusion
Secondary	Disease control rate, DCR	The percentage of patients with remission and stable disease after treatment in the total evaluable cases.	From Day 28 CD19/BCMA CAR-T infusion up to 2 years
Secondary	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	24 months post CD19/BCMA CAR-T cells infusion
Secondary	Progression-free survival, PFS	The time from cell reinfusion to the first assessment of disease progression or death from any cause	24 months post CD19/BCMA CAR-Tcells infusion
Secondary	Overall survival, OS	The time from the cell reinfusion to death due to any cause	From CD19/BCMA CAR-T infusion to death,up to 2 years