A Clinical Study of CD19/BCMA CAR-T Cells in the Treatment of Refractory POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, and Vasculitis

Study Overview
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Brief Summary
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A Clinical Study on the Safety and Effectiveness of CD19/BCMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, and Vasculitis

Detailed Description
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POEMS syndrome, amyloidosis, autoimmune hemolytic anemia, vasculitis and other diseases may only show local pathological damage or systemic lesions. If they are not diagnosed and treated in time or poorly controlled, they will progress as the course of the disease progresses. Risk of disability or even death.

Official Title
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A Clinical Study on the Safety and Effectiveness of CD19/BCMA Chimeric Antigen Receptor T Cells in the Treatment of Refractory POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, and Vasculitis

Conditions
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POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, Vasculitis

Intervention / Treatment
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* Biological: CD19/BCMA CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Diagnosed with POEMS syndrome, amyloidosis, autoimmune hemolytic anemia, vasculitis, and the curative effect of conventional hormones, radiotherapy and chemotherapy, protease inhibitors is not good and (or) no effective treatment means. 2. After glucocorticoids, cyclophosphamide or methotrexate treatments there are still relapsed and refractory diseases, or clearly show intolerance/toxicity to these drugs. 3. Estimated survival time> 12 weeks; 4. 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; 5. 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 arrhythm ia 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; Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids); Those who have used any gene therapy products before. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl; Those who suffer from other uncontrolled diseases are not suitable to join the study; HIV infection; Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POEMS Syndrome<br> | Biological: CD19/BCMA CAR T-cells<br>* Each subject receive CD19/BCMA CAR T-cells by intravenous infusion<br>* Other names: CD19/BCMA CAR T-cells injection;|
| Experimental: Amyloidosis<br> | Biological: CD19/BCMA CAR T-cells<br>* Each subject receive CD19/BCMA CAR T-cells by intravenous infusion<br>* Other names: CD19/BCMA CAR T-cells injection;|
| Experimental: Autoimmune Hemolytic Anemia<br> | Biological: CD19/BCMA CAR T-cells<br>* Each subject receive CD19/BCMA CAR T-cells by intravenous infusion<br>* Other names: CD19/BCMA CAR T-cells injection;|
| Experimental: Vasculitis<br> | Biological: CD19/BCMA CAR T-cells<br>* Each subject receive CD19/BCMA CAR T-cells by intravenous infusion<br>* Other names: CD19/BCMA CAR T-cells injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CD19/BCMA targeted CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after CD19/BCMA targeted CAR T-cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titer of auto-antibody Titer of auto-antibody titer of auto-antibody | In peripheral blood and bone marrow | Up to 2 years after CD19/BCMA targeted CAR T-cells infusion | 
| Overall response rate (ORR) | Proportion of subjects with complete or partial remission | Up to 2 years after CD19/BCMA targeted CAR T-cells infusion | 
| Best overall response, BOR | Assessment of ORR at ≤3 month | At ≤3 month | 
| 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 | 
| 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 | 2 years post CD19/BCMA CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19 CAR-T, BCMA CAR-T, POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, Vasculitis