| Eligibility |
Common Inclusion Criteria:
1. Age: = 18 years old and = 70 years old, male or female;
2. Positive CD19 expression in peripheral blood B cells as determined by flow cytometry;
3. The functions of important organs meet the following requirements:
1. Bone marrow hematopoietic function: a. White blood cell count = 3 x 10^9/L b.
Neutrophil count = 1 x 10^9/L (no colony-stimulating factor treatment within 2
weeks before examination); c. Hemoglobin =60g/L.
2. Liver function: ALT = 3 x ULN,AST=3 x ULN, TBIL=1.5 x ULN(excluding Gilbert
syndrome, total bilirubin = 3.0 x ULN)
3. Coagulation function: International standardized ratio (INR) = 1.5 x ULN,
prothrombin time (PT) =1.5 x ULN.
4. Cardiac function: good hemodynamic stability, left ventricular ejection fraction
(LVEF) =55%.
4. Female subjects of childbearing potential and male subjects whose partner is a female
of childbearing potential are required to use medically approved contraception or
abstain from sex for at least 6 months during and at least 6 months after the end of
the study treatment period; female subjects of childbearing potential have had a
negative serum HCG test within 7 days prior to study enrollment and are not lactating;
5. Voluntarily participate in this clinical study, sign an informed consent form, have
good compliance, and cooperate with follow-up.
Criteria for Recurrent/refractory primary membranous nephropathy
1. Primary membranous nephropathy diagnosed pathologically by renal biopsy;
2. Screening period 24-hour urine protein quantification =3.5 g;
3. Individuals who have not achieved partial remission (PR) after more than 6 months of
treatment with hormonal and/or cytotoxic drugs, immunosuppressive therapy, and/or
biologics (including but not limited to anti-CD20 monoclonal antibody); or individuals
who have relapsed again after achieving complete remission/partial remission (CR/PR)
with treatment (24h urine protein quantification =3.5g);
4. Glomerular filtration rate (eGFR, CKD-EPI formula) =45 ml/min/1.73m2 during the
screening period.
Criteria for Relapsed/refractory IgA nephropathy
1. Primary IgA nephropathy pathologically confirmed by renal biopsy;
2. Treated (ACEI/ARB analogs) for at least 3 months;
3. Treatment with hormonal and/or cytotoxic drugs, immunosuppressive therapy, and/or
biologics (including, but not limited to anti-CD20 monoclonal antibody) for more than
6 months, 24-hour urine protein quantification = 1.0 g; or rapid progression of renal
function (= 50% decrease in eGFR within 3 months); or relapse after treatment to
achieve complete remission/partial remission (CR/PR) (24-hour urine protein
quantification = 1.0 g);
4. Glomerular filtration rate (eGFR, CKD-EPI formula) =30 ml/min/1.73m2 during the
screening period.
Criteria for Relapsed/refractory ANCA-associated vasculitis
1. Meets 2022 ACR/EULAR diagnostic criteria for ANCA vasculitis, including microscopic
polyangiitis, granulomatous polyangiitis, eosinophilic granulomatous polyangiitis;
2. Positive ANCA related antibodies (MPO-ANCA or PR3-ANCA positive);
3. Renal biopsy pathology consistent with renal damage in ANCA-associated vasculitis;
4. The Birmingham Vasculitis Activity Scale (BVAS) is = 15 points (a total score of 63
points), indicating the activity of the vasculitis condition;
5. BVAS score includes at least 2 abnormalities in the renal program;
6. Definition of relapse/refractory : ineffective conventional treatment or relapse of
disease activity after remission. Definition of routine treatment: use of
glucocorticoids (more than 1 mg/kg/d) and cyclophosphamide for =3 months, and any of
the following immunomodulatory drugs: antimalarial drugs, azathioprine, mycophenolate
mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, as well as biological
agents such as rituximab and belimumab;
7. Glomerular filtration rate (eGFR, CKD-EPI formula) =15 ml/min/1.73m2 during the
screening period.
Common exclusion Criteria:
1. Individuals with known severe allergic reactions, hypersensitivity, contraindication
to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or
subjects with a history of severe allergic reactions;
2. Existence or suspicion of uncontrollable or treatable fungal, bacterial, viral or
other infections;
3. Individuals with central nervous system disorders caused by ADs or not caused by ADs
(including epilepsy, psychiatric disorders, organic encephalopathy syndromes,
cerebrovascular accidents, encephalitis, central nervous system vasculitis);
4. Individuals with relatively serious heart diseases, such as angina pectoris,
myocardial infarction, heart failure, and arrhythmia;
5. Subjects with congenital immunoglobulin deficiency;
6. Subjects with malignant tumors (except for non-melanoma skin cancer and in situ
cervical, bladder, and breast cancers that have been disease-free for more than 5
years);
7. Subjects with end-stage renal failure;
8. Subjects with positive hepatitis B surface antigen (HBsAg) or hepatitis B core
antibody (HBcAb) and HBV DNA titer in peripheral blood higher than the upper limit of
detection; Patients with positive hepatitis C virus (HCV) antibodies and positive
peripheral blood HCV RNA; People who are positive for human immunodeficiency virus
(HIV) antibodies; Those who have tested positive for syphilis;
9. Subjects with mental illness and severe cognitive impairment;
10. Subjects who have received other clinical trial treatment within 3 months;
11. Pregnant or intending to conceive women;
12. In the opinion of the investigator, there are other reasons why subjects cannot be
included in this study.
Exclusion Criteria for Recurrent/refractory primary membranous nephropathy
1. Secondary membranous nephropathy (e.g., hepatitis B, systemic lupus erythematosus,
drug-associated, malignancy-associated, etc.), or in combination with other renal
diseases confirmed by renal biopsy;
2. Type 1 or type 2 diabetes.
Exclusion Criteria for Relapsed/refractory IgA nephropathy
1. Exclude secondary IgA nephropathy, including but not limited to: anaphylactic purpura,
ankylosing spondylitis, systemic lupus erythematosus, desiccation syndrome, viral
hepatitis, cirrhosis of the liver, rheumatoid arthritis, and mixed connective tissue
disease; or in combination with other renal diseases confirmed by renal biopsy;
2. Crescentic nephritis (pathologic diagnosis of >50% crescentic bodies), micrognathic
nephropathy with IgA deposition, and other specific types of pathologic or clinical
renal disease.
Exclusion Criteria for Relapsed/refractory ANCA-associated vasculitis
1. Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2;
2. If the patient has alveolar hemorrhage invasive lung ventilation is required,
estimated to last longer than the screening period.
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