Clinical Study of BCMA/CD70-targeted CAR-T Therapy for Refractory Pediatric Rheumatic Diseases

NCT07184450 | Recruiting Phase 1

• 1 other identifier: PBC103
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated trial to evaluate the efficacy and safety of BCMA/CD70-targeted CAR-T in the treatment of refractory pediatric rheumatic diseases.

Conditions

Juvenile Dermatomyositis (JDM); Polyarticular Juvenile Idiopathic Arthritis; Systemic Sclerosis (SSc); Primary Sjogren's Syndrome

Keywords

CAR-T; BCMA/CD70

Outcome Measures

Primary Outcomes (13)

• To evaluate the safety of CAR-T in the treatment of refractory pediatric rheumatic diseases [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

• The Total Improvement Score (TIS) of CAR-T in the treatment of refractory juvenile dermatomyositis [Effectiveness]

  The proportion of subjects who achieved the minimal, moderate, and major clinical response of the Total Improvement Score (TIS) within 6 months after reinfusion.

  6 months

• Minimal disease activity, inactive disease and remission of CAR-T in the treatment of refractory polyarticular juvenile idiopathic arthritis [Effectiveness]

  The proportion of subjects who achieved minimal disease activity, inactive disease and remission within 6 months.

  6 months

• Ped ACR 30/50/70/90/100 of CAR-T in the treatment of refractory polyarticular juvenile idiopathic arthritis [Effectiveness]

  The proportion of subjects who achieved Ped ACR 30/50/70/90/100 within 6 months.

  6 months

• mRSS of CAR-T in the treatment of refractory systemic sclerosis [Effectiveness]

  The changes from baseline in the modified Rodnan skin score (mRSS) within 6 months.

  6 months

• MDAI of CAR-T in the treatment of refractory systemic sclerosis [Effectiveness]

  The changes from baseline in modified disease activity index (MDAI) within 6 months.

  6 months

• EUSTAR activity index of CAR-T in the treatment of refractory systemic sclerosis [Effectiveness]

  The changes from baseline in EUSTAR activity index within 6 months.

  6 months

• CRISS of CAR-T in the treatment of refractory systemic sclerosis [Effectiveness]

  The changes from baseline in Composite Response Index (CRISS) within 6 months.

  6 months

• Minimal disease activity, inactive disease and remission of CAR-T in the treatment of refractory primary Sjogren's syndrome [Effectiveness]

  The proportion of subjects who achieved minimal disease activity, inactive disease and remission within 6 months.

  6 months

• The STAR response rate of CAR-T in the treatment of refractory primary Sjogren's syndrome [Effectiveness]

  The proportion of subjects who achieved the STAR response rate within 6 months.

  6 months

• ESSDAI of CAR-T in the treatment of refractory primary Sjogren's syndrome [Effectiveness]

  The changes from baseline in ESSDAI within 6 months.

  6 months

• clinESSDAI of CAR-T in the treatment of refractory primary Sjogren's syndrome [Effectiveness]

  The changes from baseline in clinESSDAI within 6 months.

  6 months

• ESSPRI of CAR-T in the treatment of refractory primary Sjogren's syndrome [Effectiveness]

  The changes from baseline in ESSPRI within 6 months.

  6 months

Secondary Outcomes (5)

• Cmax of BCMA/CD70 CAR-T cells [PK parameter]

  3 months

• Tmax of BCMA/CD70 CAR-T cells [PK parameter]

  3 months

• AUC28d/90d of BCMA/CD70 CAR-T cells [PK parameter]

  3 months

• The clearance degree of B cells [PD parameter]

  3 months

• CAR-T-related serum cytokines [PD parameter]

  3 months

Study Arms (1)

BCMA/CD70-targeted CAR-T

EXPERIMENTAL

The experiment was divided into two phases: dose exploration (Part A) and dose extension (Part B).In Part A, three dose groups (0.3×10\^5/kg, 1×10\^5/kg, 3×10\^5/kg) are set up, starting from the low dose group to explore the safe and effective dose.Upon the completion of Part A, 1 optimal dose is selected to enter into the Part B stage. The group will then be enrolled in 1\~2 cases to continue to validate the safety and efficacy.The enrollment of 4-11 patients is expected in the each indication of the trial.

Biological: BCMA/CD70-targetd CAR-T

Interventions

BCMA/CD70-targetd CAR-T BIOLOGICAL

Subjects underwent lymphocytetion cheotherapy and then received a single intravenous cell infusion

BCMA/CD70-targeted CAR-T

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.
• To meet the diagnostic criteria of refractory B-cell-related pediatric rheumatic diseases, including but not limited to juvenile dermatomyositis, polyarticular juvenile idiopathic arthritis, systemic sclerosis, and primary Sjogren's syndrome.
• Diagnosed as juvenile dermatomyositis(JDM) according to the criteria of Bohan and Peter, and meeting the following conditions:
• The classification criteria of RJDM must meet (1) and any one of (2)-(5): (1) Patients who are intolerant or unresponsive to glucocorticoids and at least 2 immunosuppressants, and the duration of adequate hormone therapy should be 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; (5) Repeated or persistent myasthenia(muscle MRI indicates extensive, diffuse edema or the Childhood Myositis Assessment Scale(CMAS) should be less than 48 points, and at least two of the following five core measurement indicators should have abnormal results: Physician Global Assessment(PhGA) ≥2cm, Patient Global Assessment(PtGA) ≥2cm, Disease Activity Score(DAS) ≥2 points, Childhood Health Assessment Questionnaire(C-HAQ) ≥0.25 points, muscle enzyme level \> 1.5×upper limit of normal);
• RJDM with anti-synthetase syndrome who are positive for anti-synthetase antibody and those with immune-mediated necrotizing myopathy who are positive for SRP or HMGCR antibody can be included.
• Meet the classification criteria for polyarticular juvenile idiopathic arthritis as defined by the International League of Associations for Rheumatology(ILAR) classification in 2001, and meeting the following conditions: After at least 6 months of traditional DMARDS treatment and at least one stable dose of DMARDS or biologic agent for ≥12 weeks, the disease is still active, that is, there are at least 2 active joints (defined as swollen joints; if there is no swelling, there must be limited passive range of motion, accompanied by pain during movement or joint tenderness).
• Meet the classification criteria for Systemic sclerosis (SSc) as defined by the 2013ACR/EULAR standards, and meeting the following conditions:
• Modified Rodnan Skin Score (mRSS) ≥15 points (total 51 points).
• Meet the classification criteria for primary Sjogren's syndrome as defined by the 2002 ACEG classification criteria /2016 EULAR/ACR classification criteria, and meeting the following conditions:
• Meet (1) and any one of (2)-(6): (1) For those who are intolerant or have an insufficient response to glucocorticoid (prednisone 1-2 mg/kg/d or an equivalent dose of other hormones) and at least two immunosuppressants, the duration of hormone treatment should be at least 6 months; (2) The disease progresses rapidly and/or involves organs such as the kidneys, nervous system, and lungs; (3) Repeated parotid gland swelling or repeated parotitis; (4) Recurrent rashes or skin ulcers; (5) Involvement of the blood system, repeated leukopenia, anemia or thrombocytopenia; (6) cryoglobulinemia;
• Positive for anti-SSA /Ro antibody;
• ESSDAI score ≥5 points or clinESSDAI score ≥5 points.
• Positive expression of CD19 in peripheral blood B cells determined by flow cytometry, and B cells \> 5 per/uL.
• Previously not treated with CAR-T; or recurrence or poor efficacy after previous autologous or universal CD19-targeted CAR-T treatment (evaluated by the researcher).
• The functions of important organs are basically normal:

You may not qualify if:

• Severe major organ involvement related to the primary disease, such as severe pulmonary hypertension (PHA) (mean arterial pressure \> 45mmHg).
• primary immunodeficiency or severe secondary immunodeficiency that has not been corrected.
• accompanied by serious or active or uncontrollable 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 severe arrhythmias (including multisource 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.
• Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months before screening; Acute graft-versushost 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.
• Had received live vaccine within 4 weeks prior to screening.
• Positive blood pregnancy test.
• 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; Arthritis, Juvenile; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Autoimmune Diseases; Immune System Diseases

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: September 5, 2025
• First Posted: September 19, 2025
• Study Start: September 1, 2025
• Primary Completion: March 30, 2026
• Study Completion (Estimated): September 30, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

CN (1)