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

NCT06792799 | Recruiting Early Phase 1

• 1 other identifier: 2025-SC-0002-P-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Autoimmune Diseases; Systemic Lupus Erthematosus; Multi-Drug Resistant Nephrotic Syndrome; IgAN - IgA Nephropathy

Keywords

car-nk; Multi-Drug Resistant Nephrotic Syndrome; Systemic Lupus Erthematosus; IgAN - IgA Nephropathy

Outcome Measures

Primary Outcomes (2)

• The safety of CAR-NK cell therapy in patients with B cell mediated autoimmune disease

  Incidence of Dose Limiting Toxicity (DLTs), Incidence and severity of Adverse Events (AEs) and Serious Adverse Event（SAEs）.

  1 months

• The efficiency of CAR-NK cell therapy in patients with B cell mediated autoimmune disease

  SLE: The rate of patients achieving SRI-4 response, LLDAS, or DORIS remission MDR-SRNS:Complete response and partial response rate. IgAN:partial or complete response.

  3 months

Secondary Outcomes (1)

• Effectiveness of other visit points

  6 months

Study Arms (1)

anti-CD19/BCMA CAR NK cells

EXPERIMENTAL

The study adopted a dose-escalation and expansion study design. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19/BCMA CAR NK cells infusion.

Biological: anti-CD19/BCMA CAR NK cells (KN5601)

Interventions

anti-CD19/BCMA CAR NK cells (KN5601) BIOLOGICAL

Patients will receive Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of anti-CD19/BCMA CAR NK cells (KN5601) will infused in each group using dose-escalation strategy.

anti-CD19/BCMA CAR NK cells

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients or their legal guardians must acknowledge the risks and procedures involved and subsequently provide informed consent to participate in the clinical trial.
• Predicted survival time ≥ 12 weeks;
• ECOG: 0\~2;
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% ;
• Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN;
• Lung function: No serious lung lesions, SpO2≥92%;
• Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-NK infusion;
• SLE:
• Age:≥5 years old;
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria；
• Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(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,etc,al); or Intolerant to standard treatments; or the dosage of steroid can not be reduced to 5mg/d after 6-month of routine treatment.
• SLEDAI 2K score\>6 points;
• No history of Central nervous system (CNS) disease within 60 days prior to screening;
• No history of macrophage activation syndrome (MAS) within one month prior to screening.
• MDR-SRNS

You may not qualify if:

• Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or subjects with a history of severe allergic reactions
• Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
• Subjects with grade III or IV heart failure (NYHA classification)
• Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
• Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
• Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening;
• Patients had seizure, or other active central nervous system disease;
• Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases;
• Secondary or congenital immunodeficiency.
• History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of KN5601, except for lupus (determined by the investigator)
• Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening;
• Received live vaccine within 4 weeks before screening;
• Subjects who have received B cell-targeted drug therapy within 1 month before enrollment
• Tested positive in Blood pregnancy test；

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead

Study Sites (1)

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

Hangzhou, Zhejiang, 310052, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases; Nephrotic Syndrome; Glomerulonephritis, IGA

Condition Hierarchy (Ancestors)

Immune System Diseases; Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis

Central Study Contacts

Jianhua Mao, PhD

CONTACT

13516819071; maojh88@zju.edu.cn

Qiuyu Li, MD

CONTACT

17794588355; liqiuyu1992@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 20, 2025
• First Posted: January 27, 2025
• Study Start: January 30, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: December 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)