Ignite Creation Date:
2024-05-06 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 12:50 PM
Study NCT ID:
NCT03605238
Status:
WITHDRAWN
Last Update Posted:
2019-09-19
First Post:
2018-06-29
Brief Title:
Treatment of Relapsed andor Refractory AQP4-IgG Seropositive NMOSD by Tandem CAR T Cells Targeting CD19 and CD20
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
Clinical Study of CD19CD20 tanCAR T Cells in Relapsed andor Refractory AQP4-IgG Seropositive Neuromyelitis Optica Spectrum Disorders NMOSD
Status:
WITHDRAWN
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
It was hard to recruit patients
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
CAR-T therapy was 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 systemic lupus erythematosus SLE Neuromyelitis optica spectrum disorders NMOSD that include the neuromyelitis optica NMO are a group of inflammatory disorders of the central nervous system characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord NMO is characterized by the presence of an anti-Aquaporin-4 AQP4 antibody which can only be produced by differentiation of B cells to plasma cells Because these anti-AQP4 antibodies may be pathogenic B cells recognizing AQP4 may be directly involved in the disease process as well B cells also play a role as potent antigen presenting cells in NMO NMO has the characteristics of high recurrence rate and poor prognosis In the conventional treatment options NMOSD could be treated with corticosteroids and immunosuppressive drugs immunosuppressant eg azathioprine mycophenolate mofetil rituximab But these drugs could barely completely cure NMOSD And now chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems The rationale for using CAR-T therapy in NMOSD is based on the known roles of B cells antibody production and plasma cells in the pathophysiology of NMOSD The strongest evidence of the importance of B cells in NMO comes from studies of B cell depletion most commonly with anti-CD20 monoclonal antibody rituximab Emerging evidence indicates that peripheral B cells are activated during a relapse and plasmablast production of anti-AQP4 antibodies spikes The investigators infuse tanCART1920 to completely deplete B cells The purpose of this study is to assess the safety and efficacy of this tanCART1920 in the treatment of NMOSD
Detailed Description:
This study is being conducted to assess anti-CD1920 CAR T cells safety and efficacy in treating patients with AQP4-IgG seropositive NMOSD
PRIMARY OBJECTIVES
I To assess the safety of the tanCART-1920 cells in treating NMOSD patients II Determine duration of in vivo survival of tanCART-1920 cells
SECONDARY OBJECTIVES
I To assess the efficacy of the tanCART-1920 cells in treating NMOSD patients
II The secondary outcome measures annual relapse rate ARR Expanded Disability Status Scale ScoreEDDS Best Corrected Visual Acuity Log MAR Spectral-Domain Optical Coherence Tomography SD-OCT Flash Visual Evoked Potential FVEP and Immunological assessments
OUTLINE Patients receive anti-CD1920-CAR coupled with CD137 and CD3 zeta signalling domains vector-transduced autologous T cells on days 0 in the absence of unacceptable toxicity The infusion dose is 1E5-2E6 CAR positive T cellskg and dose escalation methods obey the traditional 33 design three doses groups 1-2E5 3-6E5 1-2E6 CAR-T cells
After completion of study treatment patients are followed intensively for 6 months every 6 months for 2 years and annually thereafter for 3 years
PRIMARY OBJECTIVES
I To assess the safety of the tanCART-1920 cells in treating NMOSD patients II Determine duration of in vivo survival of tanCART-1920 cells
SECONDARY OBJECTIVES
I To assess the efficacy of the tanCART-1920 cells in treating NMOSD patients
II The secondary outcome measures annual relapse rate ARR Expanded Disability Status Scale ScoreEDDS Best Corrected Visual Acuity Log MAR Spectral-Domain Optical Coherence Tomography SD-OCT Flash Visual Evoked Potential FVEP and Immunological assessments
OUTLINE Patients receive anti-CD1920-CAR coupled with CD137 and CD3 zeta signalling domains vector-transduced autologous T cells on days 0 in the absence of unacceptable toxicity The infusion dose is 1E5-2E6 CAR positive T cellskg and dose escalation methods obey the traditional 33 design three doses groups 1-2E5 3-6E5 1-2E6 CAR-T cells
After completion of study treatment patients are followed intensively for 6 months every 6 months for 2 years and annually thereafter for 3 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None