This is a single-arm, open-label,phase I clinical study to evaluate the safety and tolerability of Inaticabtagene Autoleucel Injection in treatment of refractory systemic lupus erythematosus-related immune thrombocytopenia.
This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and tolerability of Inaticabtagene Autoleucel Injection in treatment of refractory systemic lupus erythematosus-related immune thrombocytopenia and determine the Phase II Recommended Dose (RP2D). The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation \& Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total duration of the study is 2 years from Inaticabtagene Autoleucel Injection infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Inaticabtagene autoleucel Injection, the autologous 2nd generation CD19-directed CAR-T cells, will be administered by vein. Before CAR-T infusion,patients will get a 3-4 days lymphodepletion therapy with fludarabine and cyclophosphamide.
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 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 Inaticabtagene Autoleucel Injection
The safe dosage for ITP patients will be evaluated by comprehensively assessing the Overall Response Rate (ORR) and the incidence of adverse events (AEs).
Time frame: Up to 28 days post-infusion
Overall Remission Rate (ORR)
The proportion of subjects achieving CR or PR after treatment by Inaticabtagene Autoleucel Injection.CR is defined as platelet count ≥100×10\^9/L. PR is defined as platelet count ≥30×10\^9/L and at least doubling from baseline, without active bleeding.
Time frame: Up to 6 months post-infusion
Proportion of subjects who achieved disease remission (DORIS)
The proportion of subjects to meet the following 2 criteria: 1.Clinical lupus erythematosus disease activity index (SLEDAI)=0. 2.Physician global assessment (PGA) is less than 0.5 (standard score is 0-3 points) without considering serological testing and low dose corticosteroids with a dose of ≤ 5mg/d (taking prednisone as an example) permitted. Antimalarial drugs, stable dose immunosuppressants, including biologics are allowed to be used.
Time frame: Up to 6 months post-infusion
Proportion of subjects who achieved lupus hypoactivity state (LLDAS)
The proportion of subjects to meet the following 5 criteria: 1. SLEDAI score ≤ 4, no activity of important organs, no hemolytic anemia or gastrointestinal activity; 2. Compared with previous assessments, there is no new lupus activity; 3. SELENA-SLEDAI physician overall assessment (PGA 0-3) ≤ 1 point; 4. The current dose of prednisone is ≤ 7.5mg/d; 5. Immunosuppressants and biologics with standard maintenance doses are well tolerated.
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Time frame: Up to 6 months post-infusion
Improvement in systemic lupus erythematosus scores (SELENA-SLEDAI)
0 to 4 is basically no disease activity;5 to 9 is light activity;10 to 14 is moderate activity;≥15 is considered heavy activity.
Time frame: Up to 24 months post-infusion
Changes in MOS item short from health survey(SF-36)
Time frame: Up to 24 months post-infusion
Changes in Primary Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)
Time frame: Up to 24 months post-infusion
Changes in serological markers
Changes in IgG, IgM, IgA, IgE levels compared to baseline.
Time frame: Up to 24 months post-infusion
Changes in serological markers
Changes in SLE disease serological markers (anti ds-DNA antibody, anti nuclear antibody AG, complement C3, C4) levels compared to baseline.
Time frame: Up to 24 months post-infusion
Reduction of Combination therapy evaluation
The duration of the patient's cessation or reduction of the combination therapy dose, as well as the degree of reduction in the combination therapy compared to baseline.
Time frame: Up to 24 months post-infusion