Clinical trial NCT06350110: Fourth-gen CAR T Cells Targeting BCMA/CD19 for Refractory Systemic Lupus Erythematosus (SLE)
Official title: T-cell Infusion Targeting BCMA and CD19 for Refractory/Relapsed Systemic Lupus Erythematosus (SLE) Patients With or Without Organs Involvement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus
Lupus Nephritis
Autoimmune Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Granulomatous Polyangiitis
Microscopic Polyangiitis
Systemic Sclerosis
Idiopathic Inflammatory Myopathies
Sjogren's Syndrome
Keywords: CAR-T Cell Therapy
Lead sponsor: Essen Biotech
Sponsor class: OTHER
First posted: 2024-04-05
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment

Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Prior to the infusion of CD19 and BCMA CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for the CAR-T cell therapy to effectively target and eliminate malignant B cells. Following chemotherapy, participants will receive the infusion of CD19 and BCMA CAR-T cells.

Monitoring and Follow-up:

Following the CAR-T cell infusion, patients will be subjected to rigorous monitoring to assess safety and treatment response.
Primary purpose: TREATMENT

Brief summary: This study is a preliminary investigation, with a single-group design, not randomized and transparent, focusing on treatment. Its purpose is to identify the highest dose of BH002 injection (CD19-BCMA CAR-T cells) that patients suffering from resistant systemic lupus erythematosus can tolerate.

Detailed description: Systemic lupus erythematosus (SLE) is a type of autoimmune disorder characterized by the creation of autoantibody-generating immune complexes, affecting various systems and organs.

In SLE, autoreactive B cells can self-activate and morph into plasma cells that produce a high volume of autoantibodies. These cells can also expose their own antigens to autoimmune T cells, thereby stimulating T cells and leading to the release of inflammatory substances.

Conventional treatment for SLE focuses on achieving prolonged remission. In contrast, CD19-BCMA CAR-T cells offer a potential solution by eradicating the abnormal B cells responsible for antibody production. This allows for the rebuilding of the immune system and the restoration of normal immune function in patients, potentially leading to a life free from medication. This highlights the promising potential of CAR-T therapy in treating SLE.

Eligibility criteria: Inclusion Criteria:

* 18-90 years old;
* Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria.
* SELENA-SLEDAI≥8.
* Patients with CD19+ B-cell.
* Hemoglobin≥85 g/L.
* WBC≥2.5×10\^9/L.
* NEUT≥1×10\^9/L.
* BPC≥50×10\^9/L.
* AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%.
* Adequate venous access for apheresis, and no other contraindications for leukapheresis.
* Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline.
* Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion.
* Agree to attend follow-up visits as required.
* Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative.

Exclusion Criteria:

* Renal disease: severe lupus nephritis (serum creatinine \> 2.5 mg/dL or 221 μmol/L) within 8 weeks --Prior to leukapheresis, or subjects who need hemodialysis.
* CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident \[CVA\], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts.
* Patients with serious lesions and a history of present illness of vital organs such as the heart, liver,kidney blood and endocrine system.
* Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;
* Received immunosuppressive therapy within 1 week prior to leukapheresis.
* Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus.
* Patients with syphilis infection.
* The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening.
* Received live vaccine treatment within 4 weeks prior to screening.
* Severe allergies or hypersensitivity.
* Contraindication to cyclophosphamide in combination with fludarabine.
* Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion.
* Cannula or drainage tubes other than central venous catheters.
* Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;
* Subjects with prior CD19 or BCMA-targeted therapy.
* Participated in any clinical study within 3 months prior to enrollment.
* Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS\>5yr; Cervical Cancer in situ; Bladder Cancer; Breast Cancer.

Primary outcomes:
measure: Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells
timeFrame: 28 days
Secondary outcomes:
measure: Rate of successful manufacture and expansion of the CD19/BCMA chimeric antigen receptor (CAR) T cells
timeFrame: 10-14 days after apheresis or thawing of cryopreserved peripheral blood mononuclear cell
Other outcomes:
Locations:
city: Beijing
country: China
facility: District One Hospital
state: Beijing
Study officials:
References: