UCAR-T cells targeting CD19 and BCMA for autoimmune blood disorders

Clinical Study on Safety, Efficacy, and Pharmacokinetics of Universal CAR-T Cell Injection Targeting CD19/BCMA in Subjects With Autoantibody-Mediated Autoimmune Benign Hematological Diseases

This treatment tests an off-the-shelf UCAR-T cell therapy that targets CD19 and BCMA to try to treat adults with antibody-driven blood disorders like ITP, autoimmune hemolytic anemia, and Evans syndrome.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: rituximab, CAR-T, chimeric antigen receptor
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07441525 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label investigator-initiated trial testing RD06-05 (UCAR-T) in adults with active autoantibody-mediated hematologic diseases. Participants receive lymphodepletion followed by a CAR-T infusion at an initial dose of 6 × 10^6 CAR+ T cells/kg with a planned escalation to 10 × 10^6 CAR+ T cells/kg if the Safety Review Committee recommends based on safety, PK, PD, and preliminary efficacy data. The trial will collect safety, tolerability, pharmacokinetics, pharmacodynamics, and early efficacy outcomes. Enrollment is limited to adults with adequate organ function who can comply with contraception and follow-up requirements and will be conducted at Union Hospital, Tongji Medical College in Wuhan.

Who should consider this trial

Good fit: Adults aged 18–75 with active antibody-mediated ITP, AIHA, or Evans syndrome who meet organ-function, pregnancy/contraception, and other eligibility requirements are the intended candidates.

Not a fit: Patients with severe organ dysfunction, active infection, pregnancy, non–antibody-mediated cytopenias, or who cannot undergo lymphodepletion or travel to the study center are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could produce durable remissions and reduce or eliminate the need for long-term immunosuppression in refractory autoimmune cytopenias.

How similar studies have performed: Autologous CD19-directed CAR-T has shown promising remissions in small series of refractory autoimmune cytopenias, but off-the-shelf UCAR-T targeting both CD19 and BCMA is a novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* Subjects voluntarily participate in this trial and sign the informed consent form.
* Aged ≥ 18 years and ≤ 75 years, regardless of gender.
* Organ function and laboratory tests:

  1. Liver function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × Upper Limit of Normal (ULN); Total Bilirubin (TBIL) ≤ 2 × ULN (except for Gilbert's Syndrome).
  2. Renal function: Creatinine ≤ 1.5 × ULN or Creatinine Clearance Rate ≥ 40 ml/min.
  3. Oxygen saturation (SpO2) ≥ 92% in room air at rest.
  4. Echocardiography shows Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
* Female subjects of childbearing potential must have a negative result in serum or urine pregnancy test at screening.
* Female subjects of childbearing potential must agree to use highly effective contraceptive methods from at least 28 days before the start of lymphodepletion to 12 months after reinfusion on RD06-05. Male subjects of childbearing potential must agree to use effective barrier contraceptive methods from the start of lymphodepletion to 12 months after reinfusion on RD06-05, and must not donate semen or sperm during the entire trial period.
* Subjects with primary Immune Thrombocytopenia (ITP), with a disease duration of at least \> 6 months.
* Refractory or relapsed ITP: Subjects show no response, unsustained response, or intolerance to at least 2 different categories of standard treatments (e.g., glucocorticoids, splenectomy, intravenous immunoglobulin (IVIg), thrombopoietin receptor agonists (TPO-RA), Bruton's tyrosine kinase (BTK) inhibitors, etc.); among which, subjects must have received at least one or more treatments from IVIg, TPO-RA, or BTK inhibitors. In addition, platelet counts must be \< 30,000/μL in two tests conducted within 15 days before the start of study treatment, with an interval of at least 7 days between the two tests.
* Complete blood count: Neutrophil count ≥ 1,000/µL, hemoglobin ≥ 60g/L.
* Subjects with Autoimmune Hemolytic Anemia (AIHA), including warm autoimmune hemolytic anemia (wAIHA), mixed autoimmune hemolytic anemia (mix-AIHA), and cold agglutinin disease (CAD), with a disease duration of at least \> 6 months.
* Refractory or relapsed AIHA: Subjects show no response, unsustained response, or intolerance to at least 3 lines of systemic treatments (e.g., glucocorticoids, rituximab, immunosuppressants, splenectomy, complement inhibitors, etc.).
* Laboratory evidence of hemolysis: At least one of the following conditions exists in either the screening period or any test within the past 3 months: haptoglobin below the lower limit of normal, or total bilirubin (especially indirect bilirubin) above the upper limit of normal, or lactate dehydrogenase (LDH) above the upper limit of normal, and/or elevated reticulocyte count.
* Complete blood count: Neutrophil count ≥ 1,000/µL, hemoglobin (Hb) \< 100g/L.
* Diagnosed with Evans Syndrome (ES), with a disease duration of at least \> 6 months.
* Refractory or relapsed ES: After at least 3 lines of systemic treatments (e.g., glucocorticoids, intravenous immunoglobulin (IVIg), rituximab, immunosuppressants, splenectomy, thrombopoietin receptor agonists (TPO-RA), complement inhibitors, etc.), at least one type of cytopenia (thrombocytopenia or hemolytic anemia) still shows no response, unsustained response, or intolerance.
* Laboratory evidence of active blood cell destruction: Platelet count \< 30,000/μL or manifestations of hemolysis exist during the screening period or within the past 3 months, such as haptoglobin \< lower limit of normal, or total bilirubin (especially indirect bilirubin) \> upper limit of normal, or LDH \> upper limit of normal, and/or elevated reticulocyte count.
* Definite response to at least one previous treatment:

Platelet (PLT) treatment response: Platelet count reaches ≥ 50,000/μL in at least 2 tests, with an increase of ≥ 20,000/μL compared to the baseline.

Hemoglobin (Hb) treatment response: Hb increases by ≥ 10-15 g/L or hemolysis indicators improve.

Exclusion Criteria:

* Has a coexisting autoimmune disease that may seriously interfere with the attribution of study disease activity or pose additional safety risks. However, if the subject's condition has been clinically stable for ≥ 3 months, and it is expected not to interfere with study assessments, the subject may be enrolled after confirmation by the investigator and approval by the sponsor's medical monitor (or their designee).
* Has rapidly progressive glomerulonephritis (RPGN), defined as any of the following:

  * Renal biopsy shows crescent formation in ≥ 50% of glomeruli.
  * Sustained doubling of serum creatinine level within 2 months before screening.
  * The investigator assesses that the subject has RPGN.
* Subjects with the following cardiac diseases will be excluded:

  * History of heart failure classified as New York Heart Association (NYHA) Class III or IV.
  * History of myocardial infarction, cardiovascular angioplasty or stenting, unstable angina, or other serious cardiac diseases within 12 months before enrollment.
* Has a history of severe central nervous system (CNS) diseases that may affect the subject's ability to comply with the study protocol or interfere with the accuracy of study assessments, such as: traumatic brain injury, disturbance of consciousness, epilepsy, cerebral vascular ischemia, or cerebral vascular hemorrhage.
* Has a history of malignant tumors other than cured non-melanoma skin cancer or carcinoma in situ (e.g., carcinoma in situ of the cervix, bladder, or breast), unless the subject has been disease-free for at least 3 years.
* Primary immunodeficiency.
* Has uncontrolled infection; simple urinary tract infections and upper respiratory tract infections are permitted as judged by the investigator and the sponsor's medical monitor (or their designee).
* Has a known history of infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or syphilis.
* Active or latent hepatitis B virus (HBV) infection.
* Positive results for Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA or IgM antibodies during the screening period.
* Has a history of recurrent tuberculosis or known recurrent tuberculosis.
* Has a history of previous chimeric antigen receptor T-cell (CAR-T) therapy or any other genetically modified immune cell therapy.
* Has received a live-attenuated vaccine within 4 weeks before enrollment.
* Has a history of allergy to any component of the cell therapy product.
* Has a history of hypersensitivity to tacrolimus, or has experienced ≥ Grade 3 tacrolimus-related toxicity in the past (including but not limited to neurological, gastrointestinal, hepatic, renal, or hematological toxicity), especially subjects who required hospitalization will be excluded. Other cases may be considered eligible after confirmation by the investigator and the sponsor's medical monitor (or their designee).
* Has participated in another clinical trial within 30 days before screening.
* Pregnant or lactating subjects, as well as subjects of childbearing potential who cannot take effective contraceptive measures.

Where this trial is running

Wuhan, Hubei

• Union Hospital, Tongji Medical College, Huazhong University of Science & Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Wei Xie, Attending Physician

Conditions Autoimmune Hemolytic Anemia; Primary Immune Thrombocytopenic Purpura; Evans Syndrome; UCART; CD19/BCMA; ITP; AIHA; EVANS