- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03605238
Treatment of Relapsed and/or Refractory AQP4-IgG Seropositive NMOSD by Tandem CAR T Cells Targeting CD19 and CD20
Clinical Study of CD19/CD20 tanCAR T Cells in Relapsed and/or Refractory AQP4-IgG Seropositive Neuromyelitis Optica Spectrum Disorders (NMOSD)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is being conducted to assess anti-CD19/20 CAR T cells safety and efficacy in treating patients with AQP4-IgG seropositive NMOSD.
PRIMARY OBJECTIVES:
I. To assess the safety of the tanCART-19/20 cells in treating NMOSD patients. II. Determine duration of in vivo survival of tanCART-19/20 cells.
SECONDARY OBJECTIVES:
I. To assess the efficacy of the tanCART-19/20 cells in treating NMOSD patients.
II. The secondary outcome measures: annual relapse rate (ARR), Expanded Disability Status Scale Score(EDDS), 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-CD19/20-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 cells/kg, and dose escalation methods obey the traditional 3+3 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 Type
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Beijing
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Beijing, Beijing, China, 100853
- People's Liberation of Army General Hospital (PLAGH)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Clinical diagnosis of neuromyelitis optica spectrum disorders (NMOSD) patients.
- Patients with AQP4-IgG seropositive by cell-based assay.
- Patients with corticosteroid treatment combined immunosuppressant (azathioprine or mycophenolate mofetil or rituximab) still recurrence.
- Clinical evidence of at least 2 relapses in last 12 months or 3 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the Screening.
- Best corrected visual acuity(BCVA)<20/60.
- Normal bone marrow reserve function: neutrophils>1 500/mm3, Hemoglobin > 10g/dL, Platelet count > 100 000/mm3.
- Normal liver and kidney function: Creatinine < 2.5 mg/dl, ALT (alanine aminotransferase)/AST (aspartate aminotransferase) < 3x normal, Bilirubin < 2.0 mg/dl.
- Successful test expansion of tanCART19/20 cells.
- Adequate venous access for apheresis, and no other contraindications for leukapheresis.
- Voluntary informed consent is given.
Exclusion Criteria:
- Pregnant or lactating women (The safety of this therapy on unborn children is not known, Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion).
- Any serious, uncontrolled diseases (including, but not limit to, uncontrolled active infection, active hepatitis B or hepatitis C infection, HIV infection, unstable angina pectoris, congestive heart failure, serious arrhythmia).
- Concurrent use of systemic steroids or immunosuppressant in the last two weeks.
- Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation.
- Other patients who are not suitable for CAR-T therapy judged by the biotherapy physician.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Corticosteroids & tanCART19/20
Twelve days of high-dose IV methylprednisolone to reduce acute inflammation, then infuse anti-CD19/20-CAR retroviral vector-transduced autologous derived T cells only once.
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Twelve days of high-dose IV methylprednisolone (1000mg×3 days, 500mg×3 days, 240mg×3 days, 120mg×3 days) before anti-CD19/20 CAR T cells infusion.
The dose is 1E5~2E6 anti-CD19/20-CAR positive T cells.
The cells infusion process may last for 30 min.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Occurrence of study related adverse events
Time Frame: From baseline to 12 months after
|
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment.
|
From baseline to 12 months after
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Annualized relapse rate (ARR) of NMOSD Attacks
Time Frame: Baseline, 12 months
|
Compare annualized relapse rate before and one year after initial CAR-T administration.
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Baseline, 12 months
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Change in Expanded Disability Status Scale (EDDS) Score
Time Frame: Baseline, 12 months
|
The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death) in half-point increments.
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Baseline, 12 months
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Change in Best Corrected Visual Acuity (Log MAR)
Time Frame: Baseline, 12 months
|
Visual acuity assessment through Snellen's test chart.
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Baseline, 12 months
|
Change in peripapillary retinal nerve fibre layer(pRNFL)
Time Frame: Baseline, 12 months
|
Compared pRNFL before and one year after initial CAR-T administration.
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Baseline, 12 months
|
Change in macular ganglion cell-inner plexiform layers (mGCIPL)
Time Frame: Baseline, 12 months
|
Compared mGCIPL before and one year after initial CAR-T administration.
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Baseline, 12 months
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Change in Flash Visual Evoked Potential (FVEP)
Time Frame: Baseline, 12 months
|
Compared FVEP before and one year after initial CAR-T administration.
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Baseline, 12 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
in vivo existence of tanCART19/20
Time Frame: Baseline, 12 months
|
RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/20 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.
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Baseline, 12 months
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Determination of serum immunoglobulins
Time Frame: Baseline, 12 months
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Compare serum IgG level before and one year after initial CAR-T administration.
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Baseline, 12 months
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Determination of serum AQP4 antibodies
Time Frame: Baseline, 12 months
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Compare serum AQP4-ab titers before and one year after initial CAR-T administration.
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Baseline, 12 months
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Determination of serum cytokines
Time Frame: Baseline, 12 months
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Compare serum cytokines before and one year after initial CAR-T administration.
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Baseline, 12 months
|
Counts of peripheral blood B cell subsets
Time Frame: Baseline, 12 months
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Compare peripheral blood B cells before and one year after initial CAR-T administration.
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Baseline, 12 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Quangang Xu, PhD, Chinese PLA General hospital
- Principal Investigator: Huanfen Zhou, PhD, Chinese PLA General hospital
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHN-PLAGH-NO-S2018-002-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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