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

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05263817

Collaborator

Yake Biotechnology Ltd. (Industry)

Enrollment

Location

Arms

35.8

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
POEMS Syndrome Amyloidosis Autoimmune Hemolytic Anemia Vasculitis	Biological: CD19/BCMA CAR T-cells	Early Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 8, 2021

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: POEMS Syndrome	Biological: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Names: CD19/BCMA CAR T-cells injection
Experimental: Amyloidosis	Biological: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Names: CD19/BCMA CAR T-cells injection
Experimental: Autoimmune Hemolytic Anemia	Biological: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Names: CD19/BCMA CAR T-cells injection
Experimental: Vasculitis	Biological: CD19/BCMA CAR T-cells Each subject receive CD19/BCMA CAR T-cells by intravenous infusion Other Names: CD19/BCMA CAR T-cells injection

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

After glucocorticoids, cyclophosphamide or methotrexate treatments there are still relapsed and refractory diseases, or clearly show intolerance/toxicity to these drugs.
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.