CAR-T for Autoimmune Hemolytic Anemia Patients Who Have Failed Three or More Lines of Therapy
The Safety and Efficacy of ThisCART19A for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy.
To Evaluate the Safety and Efficacy of ThisCART19A for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a phase 1, single-arm, open-label, dose-escalation and dose-expansion study. The main purpose is to evaluate the safety and tolerability, efficacy, pharmacokinetics and pharmacodynamics of ThisCART19A in patients with autoimmune hemolytic anemia who have failed ≥3 lines of therapy, which include glucocorticoids, rituximab, cyclophosphamide, azathioprine, fludarabine, cyclosporine, mycophenolate mofetil, BTK inhibitors, splenectomy, etc. Participants will receive ThisCART19A cell infusion after preconditioning, and they need to be closely monitored for 28 days following CAR-T cell infusion.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Tianjin Municipality
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Tianjin, Tianjin Municipality, China, 300020
- Institute of Hematology & Blood Diseases Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subject and/or subject's legal personal representative fully understand and voluntarily sign informed consent forms.
- Male or female age ≥ 12 years.
- ECOG performance status ≤2.
- Diagnosis of warm antibody hemolytic anemia (AIHA), cold AIHA, mixed AIHA or Evans syndrome.
- Hemoglobin<100g/L.
- Failure or intolerance to at least 3 lines of therapy, including glucocorticoids, rituximab, cyclophosphamide, azathioprine, fludarabine, cyclosporine, mycophenolate mofetil, Bruton's tyrosine kinase inhibitors, splenectomy.
- Laboratory tests of adequate organ function: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥40ml/min; Absolute neutrophil count (ANC) ≥1.0×10^9/L (growth factors such as granulocyte colony-stimulating factor [G-CSF] were not received within 7 days before the screening period); Left ventricular ejection fraction (LVEF) ≥45%; Blood oxygen saturation (SpO2) ≥92%.
- Subjects of childbearing potential will be required to follow contraception requirements from the time of enrollment until the end of the 6-month safety follow-up period. Female subjects of childbearing potential must have a negative Serum HCG test within 7 days before enrollment and not in the lactation period.
Exclusion Criteria:
- Clear diagnosis of lymphoproliferative tumor.
- The platelet count in peripheral blood during the screening period is <20×10^9/L.
- Have a history of severe drug allergy or allergic constitution.
- Have a history of any of the following diseases: craniocerebral trauma, consciousness disorder, epilepsy, cerebrovascular ischemia, cerebrovascular, and hemorrhagic diseases within 6 months before enrollment.
- Have any of the following serious cardiovascular diseases: myocardial infarction within 6 months before enrollment, cardiac angioplasty or stent implantation); Unstable angina; Severe cardiac arrhythmias; History of severe nonischemic cardiomyopathy; Congestive heart failure (New York Heart Association [NYHA] Class III or IV)).
- Have malignant tumors within 5 years before enrollment, unless any of the following conditions: fully treated cervical carcinoma in situ, fully treated basal cell or squamous epithelial cell skin cancer, localized prostate cancer after radical mastectomy, breast ductal carcinoma in situ after radical mastectomy, Carcinoma in situ in other locations one year after radical resection, and these diseases have no evidence of relapse.
- Subjects with any serious active fungal, bacterial, viral, tuberculosis or other infections, including active hepatitis B (defined as serum HBV-DNA ≥ 2000 IU/mL), active hepatitis C virus (Hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) antibody-positive or active syphilis patients, etc. Subjects whose HBV-DNA < 2000 IU/mL can be included on the condition that they receive antiviral drugs and monitor the related indicators during the study.
- Have mental illness and severe cognitive impairment.
- Have a history of live attenuated vaccines within 4 weeks before enrollment.
- Subjects considered to be ineligible for the study by the investigator for reasons other than the above.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: ThisCART19A
ThisCART19A comprises of allogeneic T-cells, which are genetically engineered to express chimeric antigen receptor (CAR) and targets cells expressing CD19. |
Participants will receive ThisCART19A cell infusion after preconditioning, and they need to be closely monitored for 28 days following CAR-T cell infusion.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The incidence and frequency of treatment-emergent adverse events
Time Frame: Within 6 months
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Within 6 months
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Maximal Tolerable Dose(MTD)
Time Frame: Up to 28 days after infusion
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MTD is classified by the NCI CTCAE V5.0 |
Up to 28 days after infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Best response rate (BOR) of each dose group
Time Frame: Within 12 weeks after infusion
|
BOR is determined as the most favorable response observed after cell infusion, until either disease relapse or the completion of a specified observation period. |
Within 12 weeks after infusion
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Objective response rate (ORR)
Time Frame: Within 4 weeks after infusion
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Percentage of patients with hematological response |
Within 4 weeks after infusion
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Time to response (TTR)
Time Frame: Within 6 months
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TTR is defined as the duration from cell infusion to the achievement of a hematological response |
Within 6 months
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IIT2023077
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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