Universal (allogeneic) CAR T-cell therapy targeting CD19 and BCMA for relapsed/refractory autoimmune hemolytic anemia

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

This trial will try a single infusion of universal anti‑CD19/BCMA CAR T-cells for people aged 10 and up whose autoimmune hemolytic anemia has not responded to at least three prior treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 10 Years and up
• Sex: All
• Sponsor: The Second Hospital of Anhui Medical University (Academic / other)
• Drugs / interventions: rituximab, daratumumab, cyclophosphamide, fludarabine, CAR T
• Locations: 1 site (Hefei)
• Trial ID: NCT07530380 on ClinicalTrials.gov

What this trial studies

This investigator‑initiated early phase 1 trial gives a single intravenous dose of universal (allogeneic) anti‑CD19/BCMA CAR T-cells following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Eligible patients are age ≥10 with AIHA refractory after ≥3 treatment lines and with flow cytometry–confirmed CD19 or BCMA expression on B cells. Participants will be monitored closely for safety and response, with an interim analysis after the 12‑week post‑infusion visit. The main goals are to define safety, tolerability, and preliminary signs of hematologic response.

Who should consider this trial

Good fit: People aged 10 or older with AIHA (including warm, cold, or mixed types) who have failed at least three prior lines of therapy and have CD19 or BCMA expression on B cells are the intended candidates.

Not a fit: Patients lacking CD19 or BCMA expression, those with active uncontrolled infections or severe organ dysfunction, or patients earlier in their disease course with fewer than three prior therapies are unlikely to benefit.

Why it matters

Potential benefit: If effective, this approach could induce durable remissions and reduce the need for transfusions and long‑term immunosuppression in patients with refractory AIHA.

How similar studies have performed: Autologous anti‑CD19 CAR T therapies have shown occasional success in autoimmune cytopenias, but universal allogeneic CD19/BCMA CAR T for AIHA is largely novel and untested in larger series.

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:

  1. The bone marrow function needs to meet: a Neutrophil count ≥ 1.0

     × 10 \^ 9/L; b. Platelets ≥ 30 × 10 \^ 9/L.
  2. Liver function: ALT ≤ 3 × UL; AST ≤ 3×ULN# Total bilirubin ≤ 2.0 × ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN).
  3. 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

Where this trial is running

Hefei

• The Second Hospital of Anhui Medical University — Hefei, China (Recruiting)

Study contacts

• Principal investigator: Zhai — The Second Hospital of Anhui Medical University
• Study coordinator: Zhimin Zhai, PhD

Conditions AIHA - Warm Autoimmune Hemolytic Anemia; UCART; AIHA