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

• ClinicalTrials.gov Identifier: NCT05085444
• Recruitment Status: Recruiting
• First Posted: October 20, 2021
• Last Update Posted: October 20, 2021
• Sponsor: Zhejiang University
• Collaborator: Yake Biotechnology Ltd.
• Information provided by (Responsible Party): He Huang, Zhejiang University

Tracking Information

• First Submitted Date: October 11, 2021
• First Posted Date: October 20, 2021
• Last Update Posted Date: October 20, 2021
• Actual Study Start Date: October 8, 2021
• Estimated Primary Completion Date: October 8, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2021)

• Dose-limiting toxicity (DLT) [ Time Frame: Baseline up to 28 days after CD19/BCMA CAR T-cells infusion ]
  Adverse events assessed according to NCI-CTCAE v5.0 criteria
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 90 days after CD19/BCMA CAR T-cells infusion ]
  Incidence of treatment-emergent adverse events [Safety and Tolerability]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 11, 2021)

• Concentration of CAR-T cells [ Time Frame: From admission to the end of the follow-up, up to 2 years ]
  In peripheral blood
• Objective Response Rate, ORR [ Time Frame: In 3 months of CD19/BCMA CAR-T cell infusion ]
  Proportion of subjects with complete or partial remission
• Disease control rate, DCR [ Time Frame: From Day 28 CD19/BCMA CAR-T infusion up to 2 years ]
  The percentage of patients with remission and stable disease after treatment in the total evaluable cases.
• Duration of remission, DOR [ Time Frame: 24 months post CD19/BCMA CAR-T cells infusion ]
  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 [ Time Frame: 24 months post CD19/BCMA CAR-Tcells infusion ]
  The time from cell reinfusion to the first assessment of disease progression or death from any cause
• Overall survival, OS [ Time Frame: From CD19/BCMA CAR-T infusion to death，up to 2 years ]
  The time from the cell reinfusion to death due to any cause

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Scleroderma
• Autoimmune Diseases

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

Study Arms

Experimental: Treatment of Scleroderma

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

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 11, 2021): 9
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 8, 2024
• Estimated Primary Completion Date: October 8, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: He Huang, PhD; 86-13605714822; hehuangyu@126.com

Contact: Yongxian Hu, PhD; 86-15957162012; huyongxian2000@aliyun.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05085444
• Other Study ID Numbers: CD19/BCMA-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: He Huang, Zhejiang University
• Original Responsible Party: Same as current
• Current Study Sponsor: Zhejiang University
• Original Study Sponsor: Same as current
• Collaborators: Yake Biotechnology Ltd.

Investigators

• Principal Investigator: He Huang, PhD; First Affiliated Hospital of Zhejiang University

• PRS Account: Zhejiang University
• Verification Date: October 2021