Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06371040
Other study ID # V1.0, CART-20230619
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received
Last updated
Start date May 1, 2024
Est. completion date December 1, 2026

Study information

Verified date April 2024
Source Tang-Du Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 12
Est. completion date December 1, 2026
Est. primary completion date March 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria: - Study participants will be selected for this study only if they meet all of the following criteria: 1. Age =18 years old and =80 years old; 2. The subject signs the informed consent form, is willing and able to comply with the protocol, complete the research assessment and return for follow-up; 3. To be diagnosed as a patient with systemic MG, the patient is required to have positive myasthenia-related antibodies (AChR-Ab, Musk-Ab or LRP4) on the basis of typical myasthenic symptoms; 4. Evaluated by the researcher as refractory MG. Refractory MG is defined as: 1. Treatment failed after receiving at least 2 immunosuppressants 2. Definition of treatment failure: 1) Persistent weakness and impairment of daily activities; 2) MG aggravation and/or crisis during treatment; 3) Intolerance to immunotherapy due to side effects or comorbidities; 3. Repeated plasma exchange (PE) or intravenous immune globulin (IVIg) treatment is required to control symptoms; 4. The researchers believe that despite the current routine immunotherapy for patients, MG still imposes a large functional burden on patients. 5. MGFA classification IIa~IVa at screening and baseline; 6. QMGS score =11 points or MG-ADL score =5 points at screening and baseline, of which the eye score accounts for no more than 50%; 7. Male study participants must agree to take contraceptive measures during the treatment period and within 1 year after receiving study treatment, and are prohibited from donating sperm throughout the study period; 8. If you are a woman of childbearing potential (WOCBP), you must agree to take contraceptive measures during treatment and for at least 1 year after receiving study treatment. Participants must have a negative serum pregnancy test result during screening; a negative urine pregnancy test result must be confirmed before receiving CART for the first time. Exclusion Criteria: - Prior to screening and the baseline visit, study participants will not be eligible for inclusion in the study if they meet any of the following criteria: 1. The researcher believes that there is any medical or mental condition that may harm the research participant or affect the research participant's ability to participate in this study; or any condition that the researcher believes is related to poor compliance; 2. Women who are lactating or pregnant, or women who plan to become pregnant at any time within 12 months after receiving CART treatment, or who have a history of spontaneous abortion or induced abortion within 4 weeks before screening; 3. Study participants have clinically relevant active infections (such as sepsis, pneumonia or abscess) or serious infections (resulting in hospitalization or requiring antibiotic treatment) within 4 weeks before screening; 4. thymoma that underwent thymectomy within 6 months before baseline or was planned to undergo thymectomy during the study, or required chemotherapy and/or radiotherapy at any time; 5. Investigator participants have received live attenuated vaccine vaccination within 8 weeks before screening; or plan to receive live vaccine vaccination within 8 weeks after treatment; 6. Study participants have received rituximab treatment within 6 months before screening; 7. Have received tocilizumab or eculizumab treatment within 3 months before screening; 8. Have received intravenous human immunoglobulin, plasma exchange, or immunotherapy within 4 weeks before screening; 9. Those with known serious underlying diseases, such as liver and kidney damage, blood diseases, previous severe cardiovascular disease, severe hypertension, diabetes, and poor blood pressure and blood sugar control; 10. Unresected thymoma (Note: Subjects with benign thymoma resected more than one year before screening are eligible. Benign is defined as no known metastasis on pathological examination and no intracystic or extracystic Extension. Imaging studies must be performed during the screening period to assess thymic status). 11. Any of the following laboratory abnormalities occur during the screening period (one repeat measurement can be performed during the screening period before randomization to confirm the results) 1. Elevated liver enzymes (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN)). 2. Total bilirubin>1.5 times ULN 3. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 4. Abnormal PT or INR, or prolonged APTT >1.5 times ULN 5. Neutrophil count <1000cell/ul 6. Platelet count <50000/mm3 7. Hemoglobin<8.0g/dl 12. Those with a high-risk history of tuberculosis infection or acquired tuberculosis infection; 13. Known immunodeficiency diseases, including human immunodeficiency virus (HIV) infection; 14. Positive for hepatitis B surface antigen (HBsAg) during the screening period; 15. Receive blood transfusion treatment 4 weeks before screening or during the screening period; 16. Symptoms worsen rapidly during the lead-in period and enter crisis or pre-crisis state (MGFA IVb-V) 17. Other circumstances in which the researcher deems it inappropriate to participate in the study.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
CD19-BCMA Targeted CAR-T Dose 1
5.0 e5/ kg CD19-BCMA CAR-T positive T cells
CD19-BCMA Targeted CAR-T Dose 2
1.5 e6/ kg CD19-BCMA CAR-T positive T cells
CD19-BCMA Targeted CAR-T Dose 2
5 e6/ kg CD19-BCMA CAR-T positive T cells

Locations

Country Name City State
China Tangdu Hospital, The Fourth Military Medical University Xi'an Shaanxi

Sponsors (1)

Lead Sponsor Collaborator
Ting Chang, MD

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Other Changes in proportion of peripheral blood immune cell Changes in proportion of peripheral blood immune cell subsets of subjects after infusion of CD19-BCMA CAR-T From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Other serum inflammatory markers levels The levels of biomarkers used to evaluate safety and efficacy after infusion of CD19-BCMA CAR-T (ie, serum cytokine levels, serum inflammatory markers, plasma BCMA levels). Cytokines include at least IFN?, IL-6, Soluble gp130, soluble IL-6R, TNFa, IL-2 and IL-10, other biomarkers and cytokines will be added based on the literature From Baseline (Day 1) up fo Follow-Up (up to 4 weeks)
Primary Frequency, 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 From Baseline (Day 1) to Safety Follow-Up Visit (up to 4 weeks)
Secondary 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) From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary Changes of blood pressure From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary Changes of pulse rate From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary Changes of weight From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary 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 From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary 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 From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary 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 From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary 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]) From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary 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]) From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary 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 From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
Secondary Changes of immunoglobulins Changes in immunoglobulins (IgG, IgM, IgA, IgE) within 24 weeks after CD19-BCMA CAR-T infusion From Baseline (Day 1) up fo Follow-Up (up to 24 weeks)
See also
  Status Clinical Trial Phase
Completed NCT05039190 - Evaluate the Efficacy and Safety of HBM9161(HL161)Subcutaneous Injection in Patients With Generalized MG Patients Phase 3
Recruiting NCT04561557 - Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System Early Phase 1
Completed NCT01727193 - The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy Phase 3
Completed NCT00285350 - Mycophenolate Mofetil in Myasthenia Gravis Phase 3
Recruiting NCT05890833 - The Risk of Falls Index for Patients With Neuromuscular Disorders
Completed NCT05694234 - Influences of Sugammadex on Postoperative Progress in Patients With Myasthenia Gravis Undergoing Video-assisted Thoracoscopic Thymectomy: Retrospective Study
Recruiting NCT05635266 - Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
Not yet recruiting NCT04965987 - Oxaloacetate in Myasthenia Gravis Phase 1
Not yet recruiting NCT05095103 - Immune Profiles in Myasthenia Gravis
Completed NCT02066519 - Benefits and Tolerance of Exercise in Patients With Generalized and Stabilized Myasthenia Gravis N/A
Terminated NCT02102594 - Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB) Phase 2
Completed NCT02774239 - A Pilot Trial To Assess The Feasibility And Efficacy Of SCIG In Patients With MG Exacerbation (SCIG-MG) Phase 3
Completed NCT02118805 - Innovative Measures of Speech and Swallowing Dysfunction in Neurological Disorders
Terminated NCT01828294 - Subcutaneous Ig Maintenance Therapy for Myasthenia Gravis Phase 1
Terminated NCT00727194 - Safety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis Phase 2
Completed NCT04590716 - Help Build an A.I. Model to Predict Myasthenia Gravis Symptom Patterns and Flares
Recruiting NCT04837625 - Study of Myasthenic Crisis in China
Not yet recruiting NCT01469858 - Perception and Multisensory Integration in Neurological Patients Using fMRI N/A
Completed NCT05408702 - Exercise in Autoimmune Myasthenia Gravis and Myasthenic Syndromes
Completed NCT03205306 - Myasthenia Gravis and Psyche