Clinical trial NCT06212154: CAR-T for Autoimmune Hemolytic Anemia Patients Who Have Failed Three or More Lines of Therapy
Official title: The Safety and Efficacy of ThisCART19A for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Autoimmune Hemolytic Anemia
CD19 CAR-T Cell Infusion
Keywords: ThisCART19A
Autoimmune Hemolytic Anemia
Relapsed/refractory after receiving three or more lines of therapy
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Suzhou Fundamenta Therapeutics
First posted: 2024-01-18
Enrollment: 13
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To Evaluate the Safety and Efficacy of ThisCART19A for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence and frequency of treatment-emergent adverse events
timeFrame: Within 6 months
measure: Maximal Tolerable Dose(MTD)
timeFrame: Up to 28 days after infusion
Secondary outcomes:
measure: Best response rate (BOR) of each dose group
timeFrame: Within 12 weeks after infusion
measure: Objective response rate (ORR)
timeFrame: Within 4 weeks after infusion
measure: Time to response (TTR)
timeFrame: Within 6 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
References: