Clinical trial NCT03030976: A Study of CD19 Redirected Autologous T Cells for CD19 Positive Systemic Lupus Erythematosus (SLE)
Official title: An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: CD19
CAR-T
SLE
Lead sponsor: Shanghai GeneChem Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: RenJi Hospital
First posted: 2017-01-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of the central nervous system). SLE is a kind of autoimmune diseases which involving multiple systems, organs and with the present of a variety of autoantibodies. In the conventional treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells in the treatment of SLE.

Detailed description: This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of systemic lupus erythematosus (SLE) patients
* Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry
* Age: 18-69 years old
* Creatinine \< 1.5 mg/dl
* cardiac ejection fraction\>55%
* hemoglobin\>9g/dL
* Bilirubin \<2.0 mg/dl
* Successful test expansion of T-cells
* Adequate venous access for apheresis, and no other contraindications for leukapheresis
* Voluntary informed consent is given

Exclusion Criteria:

* Pregnant or lactating women
* Uncontrolled active infection
* Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
* Previously treatment with any gene therapy products
* Feasibility assessment during screening demonstrates\<5% transduction of target lymphocytes, or insufficient expansion (\<5-fold) in response to CD3/CD28 costimulation
* Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, serious arrhythmia)

Primary outcomes:
measure: Safety of CAR-T cell（i.v.）by number of patients with adverse event
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of patients with tumor response
timeFrame: 8 weeks
measure: 3. Detection of transferred T cells in the circulation using quantitative -PCR
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine, Renji Hospital
Study officials:
affiliation: RenJi Hospital
name: Qiang Guo, Doctor
role: PRINCIPAL_INVESTIGATOR
References: