Efficacy and Safety of CD19 UCAR T Cells in Refractory Systemic Lupus Erythematosus

NCT06691152 | Recruiting Phase 1 DMC

• 1 other identifier: PBC078
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial to evaluate the safety and efficacy of CD19 Universal CAR-T cells in the treatment of refractory systemic lupus erythematosus.

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus; CAR T-Cells; Pediatrics

Outcome Measures

Primary Outcomes (1)

• Adverse events related to CD19 universal CAR-T cells

  Incidence and severity of AEs associated with CD19 universal CAR-T cells as assessed by CTCAE v5.0

  3 months

Secondary Outcomes (4)

• Proportion of patients achieving DORIS remission after CD19 universal CAR-T infusion

  6 months

• Proportion of patients achieving low disease activity status (LLDAS) after CD19 universal CAR-T infusion

  3 months and 6 months

• Proportion of patients achieving SRI-4 remission after CD19 universal CAR-T infusion

  3 months and 6 months

• Cellular kinetics

  6 months

Study Arms (1)

CAR T cell treatment group

EXPERIMENTAL

This trial was designed as an open, single-arm, multicenter, dose-increasing trial, three dose groups (1×10\^7/kg, 3×10\^7/kg, 6×10\^7/kg) are set up, starting from the low dose group to explore the safe and effective dose.

Biological: CD19 Universal CAR-T cells

Interventions

CD19 Universal CAR-T cells BIOLOGICAL

Three dose groups (1×10\^7/kg, 3×10\^7/kg, 6×10\^7/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.

CAR T cell treatment group

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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); or Intolerant to standard treatments;
• SLEDAI 2K score≥8 points;
• The functions of important organs are basically normal:
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2； 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%;
• Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
• Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
• Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

You may not qualify if:

• Received CAR T cell therapy previously;
• Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
• Active tuberculosis at the time of screening;
• 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；
• Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
• Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
• History of organ transplantation or hematopoietic stem cell transplantation, or ≥Grade 2 GVHD within 2 weeks prior to screening；
• 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;
• Received live vaccine within 4 weeks before screening;
• Tested positive in Blood pregnancy test；
• Previous or concurrent malignancy；
• Patients who participated in other clinical study within 3 months prior to enrollment;
• Any other conditions that the investigators deem it unsuitable for the study.

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, 310052, China

RECRUITING

Related Publications (4)

• Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.

  PMID: 34347960 BACKGROUND

• Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.

  PMID: 38381673 BACKGROUND

• Charras A, Smith E, Hedrich CM. Systemic Lupus Erythematosus in Children and Young People. Curr Rheumatol Rep. 2021 Feb 10;23(3):20. doi: 10.1007/s11926-021-00985-0.

  PMID: 33569643 BACKGROUND

• Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.

  PMID: 28925994 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jianhua Mao

  Children's Hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianhua Mao, Prof

CONTACT

0571-86670076; maojh88@zju.edu.cn

Xue He

CONTACT

15088688407; 6511009@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: 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: November 11, 2024
• First Posted: November 15, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)