CD19 CAR-T therapy for relapsed or refractory autoimmune diseases

CAR-T Cell Therapy in Relapsed/Refractory Autoimmune Diseases

This trial will try CD19 CAR-T cell therapy in adults with relapsed or refractory autoimmune diseases to see if it controls disease activity and allows stopping immunosuppressive drugs.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: ShenZhen Cell Valley (Industry-sponsored)
• Drugs / interventions: CAR-T
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT07193667 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-center, open-label, single-arm dose-escalation trial using retroviral tandem CD19 CAR-T cells given by intravenous infusion after lymphodepletion. Participants undergo screening, a lymphocyte-depletion pretreatment (FC regimen), CAR-T infusion, intensive early safety monitoring (days 0–28), efficacy checks through week 12, and follow-up out to about 52 weeks. The reported cohort included 15 patients (eight with severe SLE, three with idiopathic inflammatory myositis, and four with systemic sclerosis) with median follow-up of 15 months. In that cohort investigators observed remissions or major clinical responses and complete discontinuation of immunosuppressive therapy.

Who should consider this trial

Good fit: Adults aged 18–65 with relapsed or refractory autoimmune diseases who have detectable CD19+ peripheral B cells and meet the trial's organ and bone marrow function criteria are the intended candidates.

Not a fit: Patients without measurable CD19+ B cells, with significant organ dysfunction, uncontrolled infection, or who do not meet the age or safety criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this therapy could induce durable remissions and allow some patients to stop long-term immunosuppressive medications.

How similar studies have performed: A New England Journal of Medicine report of CD19 CAR-T in autoimmune disease demonstrated strong clinical responses, supporting the therapeutic potential of this approach.

Eligibility criteria

Inclusion Criteria:

* age 18-65 years (including threshold) and gender;
* positive expression of CD19 in peripheral blood B cells as determined by flow cytometry;
* the function of vital organs meets the following requirements:

  1. Bone marrow function needs to meet the following requirements: a. White blood cell count ≥3×109/L; b. Neutrophil count ≥1×109/L (no colony-stimulating factor treatment within 2 weeks prior to the examination); c. Hemoglobin ≥60g/L;
  2. Liver function: ALT≤3×ULN (except for elevated ALT caused by inflammatory myopathy); AST≤3×ULN (except for AST elevation caused by inflammatory myopathy); TBIL≤1.5×ULN (except for Gilbert's disease).

     TBIL≤1.5×ULN (except Gilbert's syndrome, total bilirubin≤3.0×ULN);
  3. Renal function: creatinine clearance (CrCl) ≥ 30 ml/minute (Cockcroft/Gault formula, except for disease-induced decline in CrCl);
  4. Coagulation: international normalized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) ≤ 1.5 x ULN.
  5. Cardiac function: hemodynamic stability;
* female subjects of childbearing potential and male subjects with a partner of childbearing potential are required to use medically approved contraception or be abstinent from sexual intercourse for at least 6 months during and after study treatment; female subjects of childbearing potential must have had a negative serum HCG test within 7 days prior to study enrollment and must not be breastfeeding;
* Voluntarily participate in this clinical study and sign the informed consent form, good compliance and cooperate with follow-up visits.
* Specific inclusion criteria:
* Relapsed refractory systemic lupus erythematosus.
* meets the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE;
* have a Disease Activity Score SLEDAI⁃2000 ≥ 6; and have at least one British Isles Lupus Assessment Group Index (BILAG-2004) Category A (severe manifestations) or two Category B (moderate manifestations) organ scores, or both; or have a Disease Activity Score SLEDAI-2000 ≥ 8;
* Definition of relapse-refractory: failure of conventional treatment for more than 6 months or recurrence of disease activity after remission.
* Relapsing Refractory/Progressive Diffuse Systemic Sclerosis
* meets the 2013 ACR's classification criteria for systemic sclerosis consistent with a diffuse presentation
* is positive for antibodies related to systemic sclerosis;
* diffuse cutaneous sclerosis manifestations or active interstitial lung disease (HRCT suggestive of ground-glass exudates);
* definition of relapsing-refractory: failure of conventional treatment for more than 6 months or recurrence of disease activity after remission.
* Definition of Progressive: Rapid cutaneous progression (\>25% increase in mRSS); or pulmonary progression (10% decrease in FVC, or \>5% decrease in FVC with 15% decrease in DLCO).
* Note: It is sufficient if one of Articles 4 and 5 is fulfilled.
* Relapsed refractory/progressive inflammatory myopathy
* meets the 2017 EULAR/ACR classification criteria for inflammatory myopathies (including DM , PM, ASS, and NM);
* is positive for antibodies to myositis;
* in those with muscle involvement, an MMT-8 score of less than 142 and abnormal findings on at least two of the following five core measurements (PhGA, PtGA, or Extramuscular Disease Activity Score ≥2; Total HAQ Score ≥0.25); Myosin level 1.5 times the upper limit of the normal range); or MMT-8 ≥142 in the presence of active interstitial lung disease (HRCT suggestive of ground-glass exudates);
* Definition of relapse refractory: failure of conventional treatment for more than 6 months or recurrence of disease activity after remission.
* Definition of progressive: the presence of exacerbation of myositis or rapidly progressive interstitial pneumonia.
* Note: It is sufficient if one of Articles 4 and 5 is fulfilled.
* Relapsed Refractory/Progressive Immune Thrombocytopenia
* meets the 2019 American Society of Hematology (ASH) classification criteria for immune thrombocytopenia;
* have bone marrow morphology characterized by increased or normal megakaryocytes with impaired maturation;
* exclude other secondary thrombocytopenia
* Definition of recurrent refractory: a patient who fails to achieve a satisfactory outcome after first-line standard therapy (e.g., glucocorticoids), including a full dose and course of therapy, i.e., platelet counts that cannot be maintained at a safe level (generally considered to be platelet counts \> 30 × 10⁹ /L and without overt bleeding symptoms).
* Definition of progressive: a sustained decline in platelet count over the course of the disease, or a progressive worsening of bleeding symptoms, which may be accompanied by signs such as splenomegaly, and a progressively worse response to conventional therapy.
* Note: It is sufficient if one of Articles 4 and 5 is fulfilled.

Exclusion Criteria:

* A history of severe drug allergies or sensitivities;
* the presence or suspicion of fungal, bacterial, viral or other infections that are uncontrolled or require treatment
* persons with central nervous system disorders caused by ADs or not caused by ADs.
* those with intolerable cardiac function;
* subjects with congenital immunoglobulin defects.
* history of malignant tumors within the last five years.
* end-stage renal failure;
* subjects with positive Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb) and peripheral blood HBV DNA titer higher than the upper limit of the test; subjects with positive antibody to Hepatitis C virus (HCV) and peripheral blood HCV RNA; subjects with positive antibody to Human Immunodeficiency Virus (HIV); and subjects with a positive test for Syphilis;
* mental illness and severe cognitive impairment;
* have participated in other clinical trials within 3 months prior to enrollment;
* immunosuppressants or biologics with a therapeutic effect for the indication within five half-lives prior to enrollment
* women who are pregnant or intend to become pregnant;
* subjects who, in the opinion of the investigator, have other reasons for not being included in the study.

Where this trial is running

Shenyang, Liaoning

• No. 155, The First Affiliated Hospital of China Medical University, Nanjing North Street, Heping District, Shenyang, Liaoning Province — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Study coordinator: rui sun

Conditions Relapsed/Refractory Autoimmune Diseases; CAR-T