This is a single center, open-label, 3+3 dose escalation, early phase 1 study to evaluate the safety, tolerability, and preliminary efficacy of PRG-1801 for patients with relapsed/refractory immune thrombocytopenia (ITP).
This investigator-initiated clinical study aims to evaluate PRG-1801, a BCMA-targeted CAR-T cell therapy, in patients with relapsed refractory immune thrombocytopenia (ITP). The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy. Approximately 1 sites are planned to be selected for the clinical trial. The subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be assigned into 100×10\^6, and 200×10\^6 CAR-T cells groups in order of sequence. And the subjects will undergo leukapheresis, lymphodepletion pre-treatment, and a single infusion of PRG-1801. Dose escalation will follow 3 + 3 design and 3-6 subjects in each group will complete a single dose. Within the same dose group, the next subject will be administered after the previous subject has completed at least 14 days of safety observation. After the last subject in each dose group has completed the dose-limiting toxicity (DLT) assessment window of 28 days after single dose, the enrollment and treatment for the next dose group may be initiated after the Safety Review Committee (SRC) agrees to enter the next dose group based on clinical safety data assessment. When DLT occurs in 1 of 3 subjects in a dose group, 3 additional subjects in the same dose group will be required (up to 6 subjects in the dose group have completed DLT assessment): if no DLT occurs in the additional 3 subjects, dose escalation will continue; if 1 of the 3 additional subjects experiences one DLT, dose escalation will be discontinued; if more than 1 of the 3 additional subjects experiences DLTs, dose escalation will be discontinued, and 3 additional subjects will be required to be enrolled at one lower dose level for DLT assessment. After the end of escalation for the maximum dose group, if no MTD is observed, the highest dose level is defined as the MTD
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
PRG-1801 is a chimeric antigen receptor T-cell (CAR-T) therapy targeting BCMA. Participants will undergo leukapheresis to collect mononuclear cells for PRG-1801 manufacturing. Prior to infusion, patients receive lymphodepletion with cyclophosphamide (250-300 mg/m2/day) and fludarabine (25-30 mg/m2/day) for 3 days. PRG-1801 is then administered as a single intravenous infusion at one of three dose levels: 100×10\^6, or 200×10\^6 CAR-T cells. Premedication with antipyretics and antihistamines is given 30-60 minutes before infusion. The infusion rate is 2-5 ml/min. Patients are monitored for safety and efficacy for up to 24 months post-infusion. Some patients may be eligible for a second infusion if they respond initially but later relapse.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
NOT_YET_RECRUITINGUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGIncidence of Treatment-related Adverse Events
Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
Time frame: Up to 28 days post-infusion
The safe dosage for a single infusion of PRG-1801
The safe PRG-1801 infusion dosage for ITP patients will be evaluated by comprehensively assessing the complete response (CR) rate and the incidence of adverse events (AEs).
Time frame: Up to 28 days post-infusion
Complete response (CR) rate or Response (R) rate of administering PRG-1801 in the treatment of relapsed/refractory ITP
CR is defined as platelet count ≥100×10\^9/L. R is defined as platelet count ≥30×10\^9/L and at least doubling from baseline, without active bleeding.
Time frame: At Day 28, Month 2, Month 3, Month 6,Month 9, Month 12, Month 18, and Month 24 post-infusion
The proliferation rate and persistence time of CAR-T cells
Evaluation of CAR-T cell expansion and persistence through measurement of CAR copy number in peripheral blood
Time frame: At baseline, Day 2, Day 6, Day 10, Day 14, Day 21, Day 28, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18, and Month 24 post-infusion
Concentration of serum sBCMA, immunoglobulins (IgG, IgM, IgA), and anti-platelet glycoprotein autoantibodies
Pharmacodynamics of PRG-1801 were assessed by evaluating changes from baseline in serum sBCMA, immunoglobulins (IgG, IgM, IgA), and anti-platelet glycoprotein autoantibodies
Time frame: At baseline, Day 28, Month 2, Month 3, Month 6,Month 9, Month 12, Month 18, and Month 24 post-infusion
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