A Phase 1 study of HBI0101 BCMA-CART in B-Cell Mediated Autoimmune Rheumatic Diseases. The goal of the study is evaluation of safety and identification of the maximum HBI0101 CART dose that may be administered safely to patients with B-cell mediated autoimmune disease.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Age: 18~80 years old; for patients aged ≥ 75 years, geriatric assessment and endorsement are required;
lack of response per SLEDAI-2k (<4 points reduction from baseline) or no improvement in BILAG domains, or
disease flare per SLEDAI-2k (≥4 points increase from baseline) or new BILAG A or ≥2 new BILAG B organ scores, or intolerance or discontinuation due to adverse effects.
Progression of skin thickening ≥ 12 over the past 6 months or Modified Rodnan skin score (mRSS) ≥15
Disqualifiers
CNS disease- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-autoimmune progressive neurologic condition or PML
Abnormal liver function: aspartate transaminase (AST) or alanine transaminase (ALT) or glutamyl transpeptidase (GGT) or alkaline phosphatase (ALP) detection value is greater than 5 times the upper limit of normal (ULN); or total bilirubin test value greater than 3 times the upper limit of normal (ULN); Exceptional: liver function disturbance due to myositis.
Cardiovascular disease: Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to leukapheresis/ moderate- severe pulmonary hypertension/ severe arrhythmia (ventricular tachycardia, ventricular fibrillation, high grade ventricular block) in the past 6 months; New York heart function class (NYHA) class III- Level IV or LVEF<45%.
Lung disease: patients with chronic lung disease with any of the following: * Oxygen saturation (SpO2) < 90% on room air * FVC≤45% of predicted or DLCO≤40% of predicted at screening. * Evidence of pulmonary hypertension as defined as estimated RVSP> 50 mmHg.
Trial design
Design model
Single group
Treatments tested in this trial
HBI0101 CART
Biological/Vaccine
HBI0101 CART is defined as autologous T cells transduced ex-vivo with anti-BCMA CAR retroviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA. The HBI0101 CART may be provided fresh or cryopreserved.
Treatment groups
120 Participants
are divided into 1 treatment group
Group A: BCMA CARTExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Part A: Establishment of the initial safety profile of HBI0101 CAR T
Incidence of adverse events (AEs) and abnormal laboratory test results used to determine the dose-limiting toxicities (DLTs).
Time frame
21 days after infusion
2
Part B: Confirmation of safety with selected dose
Incidence, severity and type of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to HBI0101 CART at the dose selected in Part A
Time frame
4 years after infusion
Secondary outcomes
1
Overall survival
Evaluation of overall survival
Time frame
3 months for up to 24 months, every 6 months for up to 48 months
2
Four-year relapse/progression free survival: All Cohorts
Relapse-free survival, defined as time from remission to documented relapse. ● Progression-free survival, defined as time from HBI0101 CART infusion to documented disease progression.
