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
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- The Second Hospital of Anhui Medical University
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Incidence of Dose-Limiting Toxicities (DLTs)
Overview
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 10 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
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;
Arms & Interventions
QT-219C Cell Injection
Universal allogeneic anti-CD19/BCMA CAR T-cells
Intervention: QT-219C Cell Injection (Biological)
Outcomes
Primary Outcomes
Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame: Day 0 to Day 28 post-infusion
The number, frequency, and severity of DLTs experienced by subjects after the first infusion of QT-219C. DLTs are defined by NCI-CTCAE 5.0 and ASTCT consensus for CRS and neurotoxicity
Incidence of Adverse Events (AEs)
Time Frame: Up to 12 Months After UCAR T-cell Infusion
Evaluation of the number, frequency, and severity of all adverse events, including Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs).
Clinical response of AIHA who have failed ≥ 3 lines of therapy
Time Frame: Up to 24 Weeks After UCAR T-cell Infusion
Rates of CR, CRi, PR, ORR
Secondary Outcomes
- Cmax of CAR-T cells [PK parameter](Within 28 Days After UCAR T-cell Infusion)
- Tmax of CAR-T cells [PK parameter](Within 28 Days After UCAR T-cell Infusion)
- AUC 0-28d of UCAR-T cells [PK parameter](Within 28 Days After UCAR T-cell Infusion)
Investigators
Zhimin Zhai
Chief of Hematology Department
The Second Hospital of Anhui Medical University