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

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05085418

Collaborator

Yake Biotechnology Ltd. (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Immune Nephritis Autoimmune Diseases Lupus Nephritis	Biological: Assigned Interventions CD19/BCMA CAR T-cells	Early Phase 1

Detailed Description

Immune nephritis is a chronic glomerular disease originating in the kidney caused by various etiologies.Clinically, secondary chronic kidney damage caused by systemic diseases such as diabetes, systemic lupus erythematosus and gout is named after its primary disease, such as diabetic nephropathy and lupus nephritis. 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.

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 systemic lupus erythematosus.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 5, 2021

Anticipated Primary Completion Date :

Nov 5, 2024

Anticipated Study Completion Date :

Nov 5, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Treatment of Immune Nephritis

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

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

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (DLT) [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) [Up to 90 days after CD19/BCMA CAR T-cells infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

Concentration of CAR-T cells [From admission to the end of the follow-up, up to 2 years]
In peripheral blood and bone marrow
Objective Response Rate, ORR [In 3 months of CD19/BCMA CAR-T cell infusion]
Proportion of subjects with complete or partial remission
Disease control rate, DCR [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 [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 [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 [From CD19/BCMA CAR-T infusion to death，up to 2 years]
The time from the cell reinfusion to death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Immune Nephritis 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:

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.