Clinical Trial of CD19-targeted CAR-T Therapy for Refractory Juvenile Dermatomyositis

NCT06569472 | Recruiting Phase 1

• 1 other identifier: PBC068
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I clinical trial to evaluate the efficacy and safety of CD19-targeted CAR-T in the treatment of refractory juvenile dermatomyositis (RJDM).The experiment was divided into two phases: dose exploration (Part A) and dose extension (Part B).

Conditions

Juvenile Dermatomyositis

Keywords

CAR-T; CD19

Outcome Measures

Primary Outcomes (3)

• To evaluate the safety of CAR-T in the treatment of refractory juvenile dermatomyositis [Safety and Tolerability]

  The incidence of adverse events after CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).including the type, frequency and severity of adverse events

  28 days

• To evaluate the efficacy of CAR-T in the treatment of refractory juvenile dermatomyositis [Effectiveness]

  Disease improvement rate: The number of subjects who achieved disease improvement as a percentage of all subjects who received transfusions.

  2month,3months

• Duration of Response (DOR) of CAR-T treatment in the treatment of refractory juvenile dermatomyositis [Effectiveness]

  DOR will be assessed from the first assessment of remission to the first assessment of recurrence or progression of the disease or death from any cause

  2 years

Secondary Outcomes (3)

• AUCS of CD19 CAR-T cells [Cell dynamics]

  3 months

• CMAX of CD19 CAR-T cells [Cell dynamics]

  3 months

• TMAX of CD19 CAR-T cells[Cell dynamics]

  3 months

Other Outcomes (2)

• To evaluate the effects of CD19-targeting CAR T cell preparations on the weight of children

  2 years

• To evaluate the effects of CD19-targeting CAR T cell preparations on the height of children

  2 years

Study Arms (1)

CD19-targeted CAR-T

EXPERIMENTAL

The experiment was divided into two phases: dose exploration (Part A) and dose extension (Part B).

Biological: CD19-targetd CAR-T

Interventions

CD19-targetd CAR-T BIOLOGICAL

Subjects underwent lymphocyte clearance chemotherapy and then received a single intravenous cell infusion

CD19-targeted CAR-T

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: ≥5 years and \<17 years old
• To meet the diagnostic criteria of JDM, four or five of the following criteria must be met:① symmetrical proximal muscle weakness; ②Characteristic skin changes, including positive dermatitis (purplish red rash on upper eyelid with periorbital edema) and Gottron papules (red patchy squamous papules on the back of knuckles); ③ The level of one muscle enzyme in serum was increased; ④ Positive myositis antibody; ⑤Electromyography shows denervation and myopathy; ⑥ Muscle biopsies showed necrosis and inflammation.
• The classification criteria of RJDM must meet ① and any of the criteria②-④: ① Patients who are intolerant or unresponsive to glucocorticoids and at least 2 immunosuppressants, adequate hormone therapy and duration of at least 6 months; ② The disease progresses rapidly and/or involves organs such as lungs, heart and gastrointestinal tract; ③ Calcification of subcutaneous or muscle and joint tissues; ④ Repeated rashes or skin ulcers.
• myositis specific antibody positive, defined as MDA-5, NXP2, TIF-1γ, Ro-52 and any other positive;
• The functions of important organs are basically normal:
• ① Cardiac function: left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram;
• ② Renal function: eGFR≥30ML/min/1.73m2;
• ③ Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0×ULN;
• ④ Lung function: Lung function is basically normal, SpO2≥92%;
• Have the criteria for simple or intravenous blood collection, and no other contraindications for cell collection;
• The subject of childbearing age has a negative urine pregnancy test result and agrees to take effective contraceptive measures during the test period until 1 year after the infusion;
• The patient or his/her guardian agrees to participate in this clinical trial and signs an informed consent indicating that he/she understands the purpose and procedure of this clinical trial and is willing to participate in the study.

You may not qualify if:

• Had previously received CAR T cell therapy;
• Have other autoimmune or rheumatic diseases other than JDM;
• primary immunodeficiency or severe secondary immunodeficiency that has not been corrected;
• accompanied by serious infectious diseases, including but not limited to active tuberculosis, latent tuberculosis infection, active viral hepatitis, etc.;
• Evidence of active malignant disease or diagnosis of malignant tumor (including hematological malignancies and solid tumors, except resected and cured skin basal cell carcinoma)
• Congenital heart disease or history of acute myocardial infarction within 6 months before screening, or severe arrhythmias (including multi-source frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with a large number of pericardial effusion, serious myocarditis, etc.; Or patients with unstable vital signs who need hypertensive drugs to maintain their blood pressure;
• suffering from other diseases that require long-term use of glucocorticoids or immunosuppressants;
• There is an active or uncontrollable infection that requires systemic treatment within 1 week prior to screening;
• Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months before screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present 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;
• Had received live vaccine within 4 weeks prior to screening;
• Positive blood pregnancy test;
• Patients with known malignant diseases such as tumors before screening;
• Patients who had participated in other clinical trials within 3 months prior to enrollment;
• Situations in which other investigators consider it inappropriate to participate in the study.

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

Children's Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Dermatomyositis

Condition Hierarchy (Ancestors)

Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Meiping Lu, M.D

  Children's Hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meiping Lu, M.D

CONTACT

13685773988; meipinglu@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 26, 2024
• Study Start: July 2, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 26, 2024

Record last verified: 2024-07

Locations

CN (1)