CAR T-cell Therapy Targeting CD19 and BCMA in Patients with AIHA Who Have Failed ≥3 Lines of Therapy.

NCT06733610 | Recruiting Phase 1

• 1 other identifier: IIT2024096
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial to evaluate the safety and efficacy of universal allogeneic anti-CD19/BCMA CAR T-cells in AIHA who have failed ≥ 3 lines of therapy.

Conditions

Autoimmune Hemolytic Anemia; CD19/BCMA CAR T-cells; Universal Allogeneic CAR T-cells

Outcome Measures

Primary Outcomes (3)

• The number and severity of dose-limiting toxicity (DLT) events

  DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, and the ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.

  Within 28 Days After UCAR T-cell Infusion

• The total number, incidence, and severity of AEs

  Up to 12 Months After UCAR T-cell Infusion

• Clinical response of AIHA who have failed ≥ 3 lines of therapy

  Rates of CR, CRi, PR, ORR

  Up to 24 Weeks After UCAR T-cell Infusion

Study Arms (1)

UCAR T-cell group

EXPERIMENTAL

Universal allogeneic anti-CD19/BCMA CAR T-cells.

Biological: universal allogeneic anti-CD19/BCMA CAR T-cells

Interventions

universal allogeneic anti-CD19/BCMA CAR T-cells BIOLOGICAL

A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells.

UCAR T-cell group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
• Patients diagnosed with AIHA, including warm antibody type, cold agglutinin disease, mixed type, and other types of AIHA, with diagnostic criteria referring to the "Chinese Adult Autoimmune Hemolytic Anemia Diagnosis and Treatment Guidelines (2023 Edition)"
• The definition of recurrent/refractory AIHA that has received at least 3 failed lines of treatment is symptomatic anemia (hemoglobin\<100g/L) that persists after a routine treatment cycle of at least 6 months and is still ineffective or reappears after disease remission. The definition of conventional treatment: treatment with glucocorticoids and/or rituximab, as well as any 1-2 or more of the following immunomodulatory drugs: cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine A, azathioprine, danazol, bendamustine, fludarabine, bortezomib, and biologics including daratumumab, BTK inhibitors, Syk inhibitors, and complement inhibitors.
• ECOG ≤ 2
• Functional requirements for major organs are as follows:
• The bone marrow function needs to meet: a Neutrophil count ≥ 1.0 × 10 \^ 9/L; b. Platelets ≥ 30 × 10 \^ 9/L.
• Liver function: ALT ≤ 3 × UL; AST ≤ 3×ULN； Total bilirubin ≤ 2.0 × ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN).
• Renal function: creatinine clearance rate (CrCl) ≥ 30 ml/min (Cockcroft/Gault formula, excluding acute CrCl decline caused by the disease itself).
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
• Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

You may not qualify if:

• Subjects with a history of severe drug allergies or allergic tendencies.
• Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections.
• Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis).
• Subjects with insufficient cardiac function
• Subjects with congenital immunoglobulin deficiencies
• History of malignancy within five years
• Subjects with end-stage renal failure
• Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA \>ULN; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing
• Subjects with psychiatric disorders and severe cognitive impairments
• Subjects who have used immunosuppressive agents or biologics with therapeutic effects on the disease within five half-life before enrollment
• Pregnant women or women planning to conceive
• Active infection, active rheumatic and immune disease, drug induced and diagnosed lymphoproliferative tumor associated secondary AIHA patients

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Xi'niao Biotech: collaborator

Study Sites (1)

Regenerative Medicine Center and Red Blood Cell Disorders Center

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Jun Shi, PhD

CONTACT

13752253515; shijun@ihcams.ac.cn

Lele Zhang, PhD

CONTACT

‭15811139278‬; zhanglele@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 13, 2024
• Study Start: December 5, 2024
• Primary Completion: February 5, 2026
• Study Completion (Estimated): December 5, 2026
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)