Clinical trial NCT05085444: 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
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Scleroderma
Autoimmune Diseases
Keywords: Scleroderma
CD19 CAR T-cell therapy
BCMA CAR T-cell therapy
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2021-10-20
Enrollment: 9
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CD19/BCMA CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 90 days after CD19/BCMA CAR T-cells infusion
Secondary outcomes:
measure: Concentration of CAR-T cells
timeFrame: From admission to the end of the follow-up, up to 2 years
measure: Objective Response Rate, ORR
timeFrame: In 3 months of CD19/BCMA CAR-T cell infusion
measure: Disease control rate, DCR
timeFrame: From Day 28 CD19/BCMA CAR-T infusion up to 2 years
measure: Duration of remission, DOR
timeFrame: 24 months post CD19/BCMA CAR-T cells infusion
measure: Progression-free survival, PFS
timeFrame: 24 months post CD19/BCMA CAR-Tcells infusion
measure: Overall survival, OS
timeFrame: From CD19/BCMA CAR-T infusion to death，up to 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, PhD
role: PRINCIPAL_INVESTIGATOR
References: