NCT06585514RecruitingPhase 1
Open-Label, Non-Randomized, Single-Arm, Phase 1/2 Study of Anti-CD19 Chimeric Antigen Receptor T Cells for Refractory Systemic Lupus Erythematosus
Beijing GoBroad Hospital2 sites in 1 country18 target enrollmentStarted: October 17, 2024Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 18
- Locations
- 2
- Primary Endpoint
- Phase I: Dose-limiting toxicity (DLT)
Study Overview
Brief Summary
The goal of this study is to evaluate the safety and efficacy of CD19 CAR T cells in the treatment of Systemic lupus erythematosus (SLE).
Detailed Description
This is a single-center, open-label, non-randomized, Phase I/II trial. Patients with refractory systemic lupus erythematosus (SLE) will receive CD19 CAR T cells. The primary objective is to learn about the safety and tolerability of CD19 CAR T cell therapy in subjects with refractory SLE and to determine the optimal biological dose (OBD) and recommend phase 2 dose (RP2D) in phase I and to learn about the efficacy CD19 CAR T-cell therapy in patients with refractory SLE in phase II. The primary endpoint is type and incidence of dose limiting toxicity (DLT) within 28 days after CD19 CAR T-cell infusion in phase I and overall response rate (ORR) in phase II. A total number of 18 subjects will be enrolled.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 3 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female, aged 3-65 years.
- •Have a diagnosis of SLE and meet the classification criteria of 2019 European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
- •Positive antinuclear antibody (ANA): ANA at a titer of ≥ 1:80 on Hep-2 cells or equivalent positive test (ever) and/or a positive anti-dsDNA serum antibody test (based on ELISA assay, ≥ 30 IU/mL).
- •Refractory SLE and/or refractory lupus nephritis (LN):
- •4.1 Refractory SLE 4.1.1 Patients received at least 7.5 mg/kg/day of prednisolone to maintain low disease activity or the SLEDAI 2K score ≥
- •4.1.2 Routine treatment is ineffective or the disease relapses after remission. Definition of routine treatment: use glucocorticoid (more than 1mg/kg/d) and cyclophosphamide for 6 months; and any of the following immunomodulatory drugs for more than 3 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biological agents such as rituximab, belizumab, or telitacicept;
- •4.2 Refractory LN 4.2.1 Diagnosis of SLE based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR), Biopsy-proven LN class III, IVa [excluding III (C), IV-S (C) and IV-G (C)] or, class V lupus nephritis combined with class III or IV, according to 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, see Appendix
- •Biopsy must be performed within 6 months before or during screening.
- •4.2.2 Refractory lupus nephritis is defined as no induced remission to treatment regimens containing at least one immunosuppressant (including glucocorticoids, CTX, tacrolimus, MME, and cyclosporine) after 3 to 6 months, accompanied by no reduction (or worsening) of proteinuria or persistent antibody positives.
- •CD19+ on B cells and continuous withdrawal of the immunosuppressive drugs for more than 1 week.
- •The blood routine lymphocyte count of the subjects is > 1 × 109/L, and there is no cell collection contraindication.
- •No severe allergy.
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0 to
- •Patients are expected to live for at least 90 days.
- •Subjects and/or their guardian must understand and sign the informed consent.
Exclusion Criteria
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Impaired consciousness or intracranial hypertension:
- •Intracranial pressure elevation was above 15 mmHg;
- •Organic encephalopathy syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis, visual impairment, and other brain lesions requiring intervention.
- •Symptomatic congestive heart failure or severe cardiac arrhythmia:
- •Previously documented left ventricular ejection fraction (LVEF) by echocardiography of <45% in the 12 months;
- •Abnormal electrocardiogram (ECG): left bundle branch block, bifascicular block or any clinically meaningful ECG abnormality;
- •Congenital long QT syndrome or prolongation of the QT interval corrected for heart rate (QTcF) ≥ 470 ms. QTcF is calculated using Fridericia's Formula;
- •Any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification;
- •Unstable or poorly controlled angina pectoris, including the prinzmetal variant of angina pectoris;
- •Myocardial infarction within 6 months.
- •Manifestations of severe respiratory system failure:
- •Hypoxemic respiratory failure: PaO2 < 60 mmHg, PaCO2 < 50 mmHg at sea level, resting and breathing air conditions;
- •Subjects with pulmonary hypertension (PH): mean pulmonary artery pressure (mPAP) ≥25 mmHg measured by right heart catheterization (RHC);
- •Subjects with hypercapnia (PaCO2 ≥ 50mmHg ) and/or ventilatory dysfunction (PH <7.25 );
- •Oxygen inhalation was required to maintain oxygen saturation;
- •Acute or chronic respiratory diseases unrelated to SLE, such as acute pneumonia and interstitial lung disease.
- •Co-existence with other malignancies.
- •Disseminated intravascular coagulation (DIC).
- •Sepsis or other uncontrollable infections: active uncontrolled systemic bacterial, viral, fungal, or parasitic infection (except for fungal nail infection) or other clinically significant active disease process.
- •Uncontrollable diabetes: after at least 3 months of diet and exercise or similar treatment, fasting blood glucose (FBG) ≥ 8.0 mmol/L, postprandial blood glucose (PBG) ≥ 15 mmol/L, and glycosylated hemoglobin (HbA1c)≥8.0%; diabetic ketoacidosis or other uncontrollable complications of diabetes.
- •Serious mental illness: alcohol or drug abuse, dementia, or any other condition that would impair the subject's ability to receive the planned treatment or to understand informed consent at the study site.
- •Apparent and active intracranial lesions on cranial magnetic resonance imaging (MRI).
- •Underwent organ transplantation, excepting SCT.
- •Pregnant females or lactation.
- •Positive test for infectious hepatitis, acquired immune deficiency syndrome (AIDS) or syphilis.
- •No peripheral blood mononuclear cells (PBMC) collection or frozen PBMC for CAR T cell manufacturing.
- •eGFR CKD-EPI < 30 ml/min/1.73m
- •Patients who are unable to discontinue immunosuppression agents for ≥7 days or whose condition recurs during discontinuation while the risk of serious adverse reactions is assessed by the investigator.
- •Any active skin disease that may interfere with the evaluation of SLE, including but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-SLE skin manifestations (e.g., cutaneous vasculopathies, peripapillary dilatation, fingertip sclerosis, rheumatoid nodules, erythema multiforme, leg ulcers), or drug-induced lupus.
Arms & Interventions
CD19 CAR
Experimental
Following the lymphodepleting treatment, patients will be treated with CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose.
Intervention: CD19 CAR-T cells (Drug)
Outcomes
Primary Outcomes
Phase I: Dose-limiting toxicity (DLT)
Time Frame: 28 days post infusion
The incidence and type of dose-limiting toxicity (DLT).
Phase I: Adverse events (AEs)
Time Frame: 30 days post infusion
The incidence and severity of adverse events (AE).
Phase II: Objective response rate (ORR)
Time Frame: 3 months and 6 months post infusion
Proportions of subjects achieving SLE Responder Index (SRI)-4 response
Secondary Outcomes
- Phase I: Objective response rate (ORR)(3 months and 6 months)
- Phase I: Long-term Adverse events (AEs)(From 30 days after CD19 CAR T infusion to 2 years)
- Phase I: Pharmacokinetics(Up to 2 years post infusion)
- Phase II: Adverse events (AEs)(2 years post infusion)
- Phase II: Pharmacokinetics(Up to 2 years post infusion)
- Phase II: Overall survival (OS) and during of response (DOR)(Up to 2 years post infusion)
Investigators
Jing Pan
Director of Dept of Hemato-Oncology and Immunotherapy
Beijing GoBroad Hospital
Study Sites (2)
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