Anti-CD19/BCMA CAR-NK Cells in Patients with B Cell Mediated Autoimmune Disease

Last updated: February 9, 2025
Sponsor: The Children's Hospital of Zhejiang University School of Medicine
Overall Status: Active - Recruiting

Phase

1

Condition

Kidney Disease

Focal Segmental Glomerulosclerosis

Nephropathy

Treatment

anti-CD19/BCMA CAR NK cells (KN5601)

Clinical Study ID

NCT06792799
2025-SC-0002-P-01
  • Ages > 3
  • All Genders

Study Summary

this is an investigator-initiated trial aimed at evaluating the efficacy and safety of anti-CD19/BCMA CAR-NK Cells in Patients With B cell mediated autoimmune disease.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patients or their legal guardians must acknowledge the risks and procedures involvedand subsequently provide informed consent to participate in the clinical trial.

  2. Predicted survival time ≥ 12 weeks;

  3. ECOG: 0~2;

  4. Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obviousabnormality in electrocardiogram;

  5. Renal function: eGFR≥30ML/min/1.73m2; (For patients with an eGFR < 30 mL/min/1.73 m²or those receiving renal replacement therapy, inclusion or exclusion in the study isdetermined at the discretion of the investigators. )

  6. Liver function: Asparagus cochinchinensis transase (AST) and AlanineAminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN;

  7. Lung function: No serious lung lesions, SpO2≥92%;

  8. Negative pregnancy test for female Subjects of childbearing age, agree to takeeffective contraceptive measures the first year after CAR-NK infusion;

SLE:

  1. Age:≥5 years old;

  2. Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria;

  3. Still in moderate to severe disease activity despite ≥3M of high doseglucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ),hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF,azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide,telitacicept, Beliumab, and rituximab); or Intolerant to standard treatments; or thedosage of steroid can not be reduced to 5mg/d after 6-month of routine treatment.

  4. SLEDAI 2K score>6 points;

  5. No history of Central nervous system (CNS) disease within 60 days prior toscreening;

  6. No history of macrophage activation syndrome (MAS) within one month prior toscreening.

MDR-SRNS

  1. Age ≥3 years old, gender unlimited;

  2. Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines and have not achieved a complete response after 12 months oftreatment with two standard doses of hormone replacement drugs with differentmechanisms of action or relapse of disease activity after remission (at least one ofthe two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus; Otherhormone replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitaceptor rituximab); Or if no remission has been achieved after 3 to 6 months of adequatetreatment with one calcineurin inhibitor, if the researcher judges that the benefitsoutweigh the risks and the patient or guardian has fully informed consent, thepatient can be considered for inclusion.Patients with other diseases, such assystemic lupus erythematosus, requiring long-term systemic treatment withglucocorticoids or immunosuppressants, may be considered for inclusion after theinvestigator determines that the benefits outweigh the risks and the patient orguardian has fully informed consent;

  3. Renal biopsy was performed and the pathological type was determined to be minimallesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);

Exclusion

Exclusion Criteria:

  1. Subjects with known severe allergic reactions, hypersensitivity, contraindication toany medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), orsubjects with a history of severe allergic reactions

  2. Uncontrollable infection, or active infection that requires systemic treatmentwithin 1 week prior to screening;

  3. Subjects with grade III or IV heart failure (NYHA classification)

  4. Have a history of congenital heart disease or acute myocardial infarction within 6months prior to screening; Or severe arrhythmias (including multisource frequentsupraventricular tachycardia, ventricular tachycardia, etc.); Or combined withmoderate to massive pericardial effusion, serious myocarditis, etc; Or patients withunstable vital signs who need hypertensive drugs;

  5. Renal replacement therapy has been or is being performed within 3 months prior totransfusion;

  6. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positiveand peripheral blood hepatitis B virus (HBV) DNA titer greater than the normalreference value range; Or hepatitis C virus (HCV) antibody positive and peripheralblood hepatitis C virus (HCV) RNA titer greater than the normal reference valuerange; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilistest positive; Or cytomegalovirus (CMV) DNA test positive;

  7. Signs of herpes or varicella-zoster virus infection (especially chickenpox,shingles) within 12 weeks prior to screening;

  8. Patients had seizure, or other active central nervous system disease;

  9. Patients with malignant diseases such as tumors before screening, or with otherserious life-threatening diseases;

  10. Secondary or congenital immunodeficiency.

  11. History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic,urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease orother major medical condition that would prevent the administration of anti-CD19 CARNK Cells (KN5501), except for lupus (determined by the investigator)

  12. Received solid organ transplantation or hematopoietic stem cell transplantationwithin 3 months prior to screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening;

  13. Received live vaccine within 4 weeks before screening;

  14. Subjects who have received B cell-targeted drug therapy within 1 month beforeenrollment

  15. Tested positive in Blood pregnancy test;

  16. Patients who participated in other clinical study within 3 months prior toenrollment;

  17. Any abnormal laboratory test results judged by the investigator to be clinicallysignificant and prevent the subject from participating in the study. Laboratory testvalues that are out of range and not of clinical significance will not be consideredas exclusion criteria

  18. Any situation judged by the investigators that may increase the risk of the subjectsor interfere with the clinical trial outcome

Study Design

Total Participants: 72
Treatment Group(s): 1
Primary Treatment: anti-CD19/BCMA CAR NK cells (KN5601)
Phase: 1
Study Start date:
January 30, 2025
Estimated Completion Date:
June 30, 2029

Study Description

Autoimmune diseases are conditions in which the immune system fails to accurately recognize normal tissues or cells, leading to the attack of organs, tissues, or cells.

Systemic lupus erythematosus (SLE) is a severe autoimmune disorder that can cause widespread damage to multiple organs and systems, ultimately resulting in disability and even death. Pediatric patients with SLE are particularly susceptible to organ damage, especially renal impairment, and typically experience a more severe and protracted disease course compared to adults. Despite advances in therapy, many patients continue to suffer from SLE. In China, only 0.76% to 25% of patients achieve drug-free or clinical remission, highlighting the urgent need for novel therapeutic approaches.

For patients with multi-drug resistant nephrotic syndrome (MDR-SRNS), who are at high risk of progressing to kidney failure, there remains no effective treatment. Therefore, there is a pressing need for new therapeutic strategies.

Since 2019, CAR T-cell therapy has shown success in treating various autoimmune diseases, including SLE, systemic sclerosis, and idiopathic inflammatory dermatomyositis. However, the widespread application of autologous CAR T-cells is limited by several factors, including their high cost and the frequent occurrence of adverse effects. Autologous CAR T-cells are personalized products, which make them expensive and less accessible. Furthermore, the risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain significant concerns.

Chimeric antigen receptor natural killer (CAR-NK) cell therapy offers a promising alternative. This adoptive cell therapy involves the genetic modification of NK cells to recognize and eliminate target cells expressing disease-related antigens. CAR-NK cells have several advantages over CAR T-cells, including a lower risk of graft-versus-host disease (GVHD) and minimal occurrence of CRS or ICANS. Additionally, CAR-NK therapy is more cost-effective, which could greatly enhance its accessibility.

Given these advantages, CAR-NK cell therapy holds potential for revolutionizing the treatment of refractory SLE and MDR-SRNS, offering new hope for patients with these challenging conditions.

Connect with a study center

  • Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000

    Hangzhou, Zhejiang 310052
    China

    Active - Recruiting

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