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: Recruiting
• Conditions: Autoimmune Hemolytic Anemia; CD19 CAR-T Cell Infusion
• Intervention / Treatment: Biological: ThisCART19A

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: Interventional
• Enrollment (Estimated): 13
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jun Shi, PhD; Phone Number: 13752253515; Email: shijun@ihcams.ac.cn
• Study Contact Backup: Name: Hong Pan, MD; Email: panhong@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Jun Shi; Phone Number: 13752253515; Email: shijun@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ThisCART19A; ThisCART19A comprises of allogeneic T-cells, which are genetically engineered to express chimeric antigen receptor (CAR) and targets cells expressing CD19.	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.; Other Names: Allogeneic CAR-T targeting CD19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence and frequency of treatment-emergent adverse events		Within 6 months
Maximal Tolerable Dose(MTD)	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	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
Objective response rate (ORR)	Percentage of patients with hematological response	Within 4 weeks after infusion
Time to response (TTR)	TTR is defined as the duration from cell infusion to the achievement of a hematological response	Within 6 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: Suzhou Fundamenta Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Autoimmune Hemolytic Anemia; ThisCART19A; Relapsed/refractory after receiving three or more lines of therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: FT400-025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No