This study is a single-center, open-label, single-arm, dose-exploration study to evaluate the safety and preliminary effectiveness of CD19-BCMA CAR-T in the treatment of refractory, generalized myasthenia gravis. The study is a dose escalation trial in adult, refractory, systemic MG patients. The Keyboard method will be used to perform dose escalation to explore the maximum tolerated dose (MTD). A total of 12 MG patients who meet the inclusion criteria are expected to be recruited.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
5.0 e5/ kg CD19-BCMA CAR-T positive T cells
1.5 e6/ kg CD19-BCMA CAR-T positive T cells
5 e6/ kg CD19-BCMA CAR-T positive T cells
Tangdu Hospital, The Fourth Military Medical University
Xi'an, Shaanxi, China
RECRUITINGFrequency, type, and severity of adverse events
Frequency, type, and severity of adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events CTCAE V5.0) occurring within 4 weeks after CD19-BCMA CAR-T infusion
Time frame: From Baseline (Day 1) to Safety Follow-Up Visit (up to 4 weeks)
Frequency, type, and severity of abnormal laboratory indicators related to treatment
Frequency, type, and severity of abnormal laboratory indicators related to treatment (according to the National Cancer Institute Common Terminology Criteria for Adverse Events CTCAE V5.0)
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of blood pressure
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of pulse rate
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of weight
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of Myasthenia Gravis Activities of Daily Living (MG-ADL) scores
Changes in MG-ADL scores \[0-24 point\] from baseline at 24 weeks after CD19-BCMA CAR-T infusion
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of Quantitative Myasthenia Gravis (QMG) scores
Changes in QMG scores \[0-39 point\] from baseline at 24 weeks after CD19-BCMA CAR-T infusion
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
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Changes of Myasthenia Gravis Composite (MGC) scores
Changes in MGC scores \[0-50 point\] from baseline at 24 weeks after CD19-BCMA CAR-T infusion
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Proportion of subjects who achieved improvement
Proportion of subjects who achieved improvement at 24 weeks after CD19-BCMA CAR-T infusion and sustained it for at least 4 weeks (clinical improvement difined as a ≥2-point reduction in the total MG-ADL score \[0-24 point\])
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Time to achieve clinical improvement
Time to achieve clinical improvement (clinical improvement difined as a ≥2-point reduction in the total MG-ADL score \[0-24 point\])
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of myasthenia gravis-specific autoantibody titers
Changes from baseline in myasthenia gravis-specific autoantibody titers over 24 weeks after CD19-BCMA CAR-T infusion
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Changes of immunoglobulins
Changes in immunoglobulins (IgG, IgM, IgA, IgE) within 24 weeks after CD19-BCMA CAR-T infusion
Time frame: From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)