CAR-T for Autoimmune Hemolytic Anemia Patients Who Have Failed Three or More Lines of Therapy

Autoimmune Hemolytic Anemia Clinical Trial

Official title:

The Safety and Efficacy of ThisCART19A for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06212154
• Other study ID #: FT400-025
• Status: Recruiting
• Phase: Phase 1
• Start date: January 20, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: Jun Shi, PhD
• Phone: 13752253515
• Email: shijun[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 13
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Autoimmune Hemolytic Anemia
• Hemolysis

Intervention

Biological:
• ThisCART19A
Participants will receive ThisCART19A cell infusion after preconditioning, and they need to be closely monitored for 28 days following CAR-T cell infusion.

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital, China	Suzhou Fundamenta Therapeutics

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence and frequency of treatment-emergent adverse events		Within 6 months
Primary	Maximal Tolerable Dose(MTD)	MTD is classified by the NCI CTCAE V5.0	Up to 28 days after infusion
Secondary	Best response rate (BOR) of each dose group	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
Secondary	Objective response rate (ORR)	Percentage of patients with hematological response	Within 4 weeks after infusion
Secondary	Time to response (TTR)	TTR is defined as the duration from cell infusion to the achievement of a hematological response	Within 6 months