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This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD19 CAR-T therapy for patients with refractory myasthenia gravis, and to evaluate the pharmacokinetics of CD19 CAR-T in patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Group | Experimental | Myasthenia Gravis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD19 CAR-T cells injection | Drug | CD19 CAR-T in the Treatment of Refractory Myasthenia Gravis |
|
| 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 CAR T-cells infusion |
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 90 days after CD19 CAR T-cells infusion |
| Maximum tolerable dose | Maximum tolerable dose | From date of initial treatment to Day 28 post CD19 CAR-T infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in serum AchR antibody titer | Changes in serum AchR antibody titer | days 7, 14, 21, 28 and 90 |
| MG-activities of daily living profile (MG-ADL) | MG-ADL Myasthenia Gravis Daily Activity Scale |
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Inclusion Criteria:
1. Age ≥18 and gender unlimited;
2. Confirmed as refractory myasthenia gravis with AchR antibody positive and accord one of the following three conditions
3. Consistent with the clinical classification of MGFA myasthenia gravis IIa-IVb (including IIa,IIb,IIIa, IIIb, IVa,IVb)
4. The baseline MG-ADL score ≥5 and the musculi oculi related score< 50 ;
5. Baseline QMG score>11;
6. Regular treatment with poor efficacy and/or lack of effective treatment means that there is still recurrence or exacerbation after treatment with conventional hormones, immunosuppressants (such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A, cyclophosphamide, etc.) or rituximabï¼›
7. The estimated survival time is more than 12 weeks;
8. Women of childbearing age who have negative urine pregnancy test before medication administration and agree to take effective contraceptive measures during the trial period until the last follow-up.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| He Huang, MD | Contact | 13605714822 | hehuangyu@126.com | |
| Yongxian Hu, MD | Contact | +8615957162012 | huyongxian2000@aliyun.com |
| Name | Affiliation | Role |
|---|---|---|
| He Huang, MD | Zhejiang University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The first affiliated hospital of medical college of zhejiang university | Recruiting | Hangzhou | Zhejiang | 310000 | China |
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| ID | Term |
|---|---|
| D009157 | Myasthenia Gravis |
| ID | Term |
|---|---|
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| Baseline up to 28 days after CD19 CAR T-cells infusion |
| MG-activities of daily living profile (QMG) | Quantitative Score for Myasthenia Gravis | Baseline up to 28 days after CD19 CAR T-cells infusion |
| Myasthenia Gravis Composite Scale (MGC) | Myasthenia Gravis Composite Scale | Baseline up to 28 days after CD19 CAR T-cells infusion |
| MG-QOL15 scale | MG-QOL15 Quality of Life Scale for Myasthenia Gravis (15 items) | Baseline up to 28 days after CD19 CAR T-cells infusion |
| D010257 | Paraneoplastic Syndromes |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009468 | Neuromuscular Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |