UCAR T-cell Therapy Targeting CD19/BCMA in Relapsed/Refractory Autoimmune Hemolytic Anemia

Official title

A Clinical Study of CD19/BCMA-Targeted Universal Allogeneic CAR-T Cell Therapy in Relapsed/Refractory Autoimmune Hemolytic Anima: Evaluating Safety and Preliminary Efficacy

Overview

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

Detailed description

This is an investigator-initiated trial to evaluate the safety and efficacy of universal allogeneic anti-CD19/BCMA CAR T-cells in autoimmune hemolytic anemia who have failed ≥ 3 lines of therapy. Study intervention consists of a single infusion of universal allogeneic CAR T-cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide. Interim analysis will be performed when participants finish the visit 12 weeks after CAR T-cell infusion.

Interventions

• Biological QT-219C Cell Injection
  A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells.

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: Day 0 to Day 28 post-infusion]
• Incidence of Adverse Events (AEs) [Time frame: Up to 12 Months After UCAR T-cell Infusion]
• Clinical response of AIHA who have failed ≥ 3 lines of therapy [Time frame: Up to 24 Weeks After UCAR T-cell Infusion]

Secondary outcome measures (3)

• Cmax of CAR-T cells [PK parameter] [Time frame: Within 28 Days After UCAR T-cell Infusion]
• Tmax of CAR-T cells [PK parameter] [Time frame: Within 28 Days After UCAR T-cell Infusion]
• AUC 0-28d of UCAR-T cells [PK parameter] [Time frame: Within 28 Days After UCAR T-cell Infusion]

Eligibility criteria

Inclusion criteria

• 1\. Age ≥ 10 years, regardless of sex;
• 2\. Flow cytometry-confirmed CD19 or BCMA positivity on B cells in peripheral blood or bone marrow;
• 3\. 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)";
• 4\. 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;
• 5\. 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).
• 6\. ECOG ≤ 2;
• 7\. 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;
• 8\. Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion criteria

• 1\. Subjects with a history of severe drug allergies or allergic tendencies;
• 2\. Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections;
• 3\. History of recurrent infections (e.g., ≥3 episodes of active infection requiring medical intervention within 6 months prior to enrollment);
• 4\. History of cytomegalovirus (CMV), Epstein-Barr virus (EBV), or fungal infections within 3 months prior to screening, or history of recurrent CMV, EBV, or fungal infections;
• 5\. Receipt of any vaccination within 12 weeks prior to enrollment, or participation in a vaccine clinical trial within 12 weeks prior to enrollment;
• 6\. Subjects with insufficient cardiac function;
• 7\. Moderate to severe congestive heart failure (New York Heart Association \[NYHA\] Class III-IV);
• 8\. Subjects with congenital immunoglobulin deficiencies;
• 9\. History of malignancy within the past 5 years (except for non-melanoma skin cancer, completely resected Stage I tumor with low risk of recurrence, treated clinically localized prostate cancer, biopsy-proven cervical carcinoma in situ or squamous intraepithelial lesion on smear, and stable papillary or follicular thyroid cancer);
• 10\. 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;
• 11\. History of organ transplantation, including but not limited to bone marrow or hematopoietic stem cell transplantation;
• 12\. Severe, progressive, uncontrolled disease of the cardiovascular, cerebrovascular, hepatic, renal, pulmonary, gastrointestinal, hematologic, endocrine, or nervous system;
• 13.Psychiatric disorder or severe cognitive impairment;
• 14\. Pregnant women or women planning to conceive
• 15\. Subjects that the investigator believes have other reasons that make them unsuitable for inclusion in this study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Hospital of Anhui Medical University — Hefei

Identifiers

NCT: NCT07530380 · QH-AY-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗