Patients with end-stage renal disease (ESRD) who require kidney transplantation but are ineligible for transplant surgery due to refractory highly sensitized HLA antibodies, and who have failed first- and second-line therapies.
Conditions
Interventions
Bispecific T cell engager treatment group1:Blinatumomab group:BiTE (CD19 x CD3 Bispecific Antibody)
Bispecific T cell engager treatment group2:Teclistamab group:BiTE (BCMA x CD3 Bispecific Antibody)
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Patients aged >=18 and =90% and a kidney transplant waiting time of >=5 years; 4. Patients with normal vital organ function, including: (1) Normal cardiopulmonary function; left ventricular ejection fraction >50% on echocardiography and oxygen saturation >94%; (2) AST/ALT =90%, or unacceptable antibodies and have not met the immunological criteria required to proceed with kidney transplantation. These patients are defined as refractory highly sensitized kidney transplant candidates;
Exclusion criteria
Exclusion criteria: 1.Patients who are considered unable to comply with the enrollment and follow-up schedule; 2.Patients with known or suspected hereditary complement deficiency; 3.Patients with central nervous system diseases, including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis, visual impairment, or cranial neuropathy requiring intervention; 4.Patients with abnormal liver function, defined as AST, ALT, or GGT >3 times the upper limit of normal, or ALP or total bilirubin >1.5 times the upper limit of normal; 5.Patients with cardiovascular disease, including a history of acute myocardial infarction or unstable angina within the past 6 months, severe arrhythmia including multifocal frequent ventricular tachycardia, ventricular tachycardia, or ventricular fibrillation, or New York Heart Association class III–IV cardiac function; 6.Patients with other uncontrolled acute or chronic diseases, such as acute pneumonia, pulmonary hypertension, diabetic ketoacidosis, or acute pancreatitis, that are clinically unstable or inadequately controlled, unrelated to renal failure, and may affect the patient's tolerance to BiTE therapy; 7.Patients with acute or chronic infection, confirmed by clinical evidence, imaging, or laboratory tests, requiring treatment within 1 month before screening or during screening, including tuberculosis, Pneumocystis infection, cytomegalovirus infection, herpes simplex virus infection, herpes zoster, or atypical mycobacterial infection; patients with HIV positivity or any other uncontrolled active infection, such as active hepatitis B or hepatitis C, will also be excluded; 8.Patients scheduled to undergo surgery or with any other medical history, such as recent sepsis, laboratory abnormality, or other condition such as poor venous access, that, in the investigator's judgment, makes them unsuitable for participation in this study; 9.Patients who have participated in any clinical study within 3 months before enrollment; 10.Patients who have previously received other T-cell engagers or who are allergic to BiTE or its components; 11.Patients who are unable to understand or follow the study protocol, or who need to use medications prohibited by the protocol; 12.Patients with current malignancy; 13.Pregnant or breastfeeding women, or women who plan to become pregnant during the study period; 14.Patients whose donor is considered unsuitable for transplantation because of poor donor condition or severe vascular malformation of the donor kidney; 15.Patients participating in another concurrent clinical study; 16.Patients who refuse to provide informed consent; 17.Patients with a history of bone marrow transplantation or solid-organ transplantation other than kidney transplantation; 18.Patients with any other clinically significant medical history or current disease that, in the investigator's judgment, may pose a risk to the participant's safety or interfere with completion of study procedures or assessment of safety and efficacy; 19.Patients who receive vaccination within 30 days after baseline; 20.Patients with any other condition that the investigator considers unsuitable for participation in the study;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants achieving the predefined composite desensitization response; | — |
Secondary
| Measure | Time frame |
|---|---|
| Calculated panel-reactive antibody level;Mean fluorescence intensity of HLA class I antibodies;Mean fluorescence intensity of HLA class II antibodies;Number of participants receiving kidney transplantation within 12 months after treatment;CD19-positive B-cell count;CD3-positive T-cell count;Number of participants with neutropenia as assessed by CTCAE version 5.0;CD8-positive T-cell absolute count;Number of participants with treatment-emergent infections;CD4-positive T-cell absolute count;Number of participants with serious adverse events;Number of participants with immune effector cell-associated neurotoxicity syndrome as assessed by the ASTCT consensus grading criteria;Number of participants with cytokine release syndrome as assessed by the ASTCT consensus grading criteria; | — |
Countries
China
Contacts
Public ContactTurun Song
West China Hospital of Sichuan University
Outcome results
None listed