Actively Recruiting

Early Phase 1
Age: 3Years +
All Genders
ID06792799

An Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA Chimeric Antigen Receptor NK Cells in Treating B Cell-related Autoimmune Diseases in Children

Led by The Children's Hospital of Zhejiang University School of Medicine · Updated on 2025-12-01

36

Participants Needed

1

Research Sites

52 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and effectiveness of anti-CD19/BCMA CAR-NK cells in patients with B cell mediated autoimmune diseases, including systemic lupus erythematosus (SLE), multi-drug resistant nephrotic syndrome (MDR-SRNS), and immunoglobulin A nephropathy (IgAN). These autoimmune conditions cause the immune system to attack the body's own tissues, leading to serious organ damage, especially in children with SLE who face severe disease progression. The study addresses the urgent need for new treatments as current therapies often fail to achieve remission or prevent kidney failure in these patients. Participants will receive a combination treatment starting with fludarabine and cyclophosphamide to prepare the body for the infusion of anti-CD19/BCMA CAR-NK cells. The treatment uses a dose-escalation strategy, meaning the doses of the CAR-NK cells will be increased gradually to assess safety and effectiveness. This investigational therapy modifies natural killer cells to target disease-related cells, offering potential advantages over existing CAR T-cell therapies, including fewer severe side effects and lower costs. During the study, participants will be monitored closely with assessments focusing on the safety of the CAR-NK cell therapy within the first month and its effectiveness after three months. Additional follow-up visits will evaluate longer-term effects over six months. Researchers will track organ function, disease activity, and any side effects through laboratory tests and clinical evaluations. The total duration of participation and detailed monitoring plans are designed to ensure thorough evaluation of this new treatment approach.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 3Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients or legal guardians must provide informed consent for participation
  • Predicted survival time of at least 12 weeks
  • ECOG performance status of 0 to 2
  • Left ventricular ejection fraction of 55% or higher
  • Estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73m2 or higher, with some exceptions at investigator discretion
  • Liver enzymes (AST and ALT) less than or equal to 3 times the upper normal limit; total bilirubin less than or equal to 2 times the upper normal limit
  • No serious lung lesions and oxygen saturation of 92% or higher
  • Negative pregnancy test for females of childbearing age and agreement to use contraception for one year after treatment
  • For SLE patients: age 5 years or older, diagnosis by 2019 criteria, moderate to severe disease despite standard treatments, SLEDAI 2K score greater than 6, no recent CNS disease or macrophage activation syndrome
  • For MDR-SRNS patients: age 3 years or older, diagnosis by 2021 KDIGO guidelines, no complete response after standard treatments or relapse, with biopsy-confirmed pathology
  • For IgA nephropathy patients: age 5 years or older, biopsy-confirmed diagnosis, prior treatment with ACE inhibitors or ARBs, and meeting specific criteria for proteinuria or eGFR decline
  • Exclusion of secondary causes and uncontrolled blood pressure for IgA nephropathy
Not Eligible

You will not qualify if you...

  • Known severe allergic reactions or contraindications to study drugs such as cyclophosphamide, fludarabine, or obinutuzumab
  • Uncontrolled or active infections requiring systemic treatment within one week before screening
  • Severe heart failure (NYHA class III or IV)
  • Recent heart disease including congenital defects, myocardial infarction within six months, severe arrhythmias, or unstable vital signs
  • Renal replacement therapy within three months before treatment
  • Positive tests for hepatitis B, hepatitis C, HIV, syphilis, or cytomegalovirus beyond normal ranges
  • Signs of herpes or varicella-zoster virus infection within twelve weeks before screening
  • History of seizures or active central nervous system disease
  • Malignant tumors or other serious life-threatening diseases
  • Secondary or congenital immunodeficiency
  • Major medical conditions that prevent administration of the study drug, except lupus
  • Recent organ or stem cell transplantation or acute graft-versus-host disease
  • Live vaccine within four weeks before screening
  • B cell-targeted therapy within one month before enrollment
  • Positive pregnancy test
  • Participation in other clinical trials within three months before enrollment
  • Clinically significant abnormal lab results
  • Any condition increasing risk or interfering with the trial as judged by investigators

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Approximately 1 week

Participants receive lymphodepletion chemotherapy followed by multiple infusions of anti-CD19/BCMA CAR NK cells using a dose-escalation strategy.

Several visits over the course of treatment including chemotherapy and CAR NK cell infusions

Follow-up

Duration - Up to 6 months

Participants are monitored to assess safety and effectiveness of the CAR-NK cell therapy.

Regular visits for safety and efficacy assessments over 6 months

Trial Site Locations

Total: 1 location

1

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

Hangzhou, Zhejiang, China, 310052

Actively Recruiting

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Research Team

J

Jianhua Mao, PhD

Q

Qiuyu Li, MD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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