Anti-Hu associated paraneoplastic neurological syndromes
Conditions
Interventions
Trade Name: Tysabri
Product Name: Tysabri (natalizumab)
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Sponsors
Erasmus University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - PEM/PSN associated with high titer (=400) anti-Hu antibodies - The neurological symptoms must still be progressing defined as neurological deterioration over the last 4 weeks - Patients aged 18 years or older - Patients with cancer related to Hu-Ab are allowed to participate - Patients who receive or will receive anti-tumor therapy are allowed to participate - Patients who have given written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: - Patients who have reached a plateau phase more than 4 weeks before inclusion date (‘damage is done’) - Patients who are unwilling to undergo lumbar puncture - Hypersensitivity to natalizumab or one of the additives - Progressive multifocal leukoencephalopathy (PML) - Immune compromised patients (patients using immunosuppressive medications other than short course of steroids) - Liver enzyme elevations of more than 5-fold normal values - Renal failure (GFR < 30 ml/min) - Active infection - Women of childbearing potential who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions. - Patients aged <18 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to investigate whether natalizumab results in functional improvement ;Secondary Objective: Secondary Objectives: neurological improvement defined as a positive score (>0) in the EFIT overall evaluation and improvement on the AMC linear disability scale, Barthel index and PNS neurological scale after three natalizumab infusions (the 12th week of natalizumab), compared to baseline. Translational Objectives: a) detection of HuD-specific T-lymphocytes in blood and CSF; b) phenotype of CSF cells (prior and after natalizumab) including B cells, T cells and DC; c) anti-HuD titers in CSF and serum; and d) single cell PCR on CSF derived plasma cells prior to treatment in order to determine the primary protein sequence of anti-HuD IgG. ;Primary end point(s): The primary endpoint is functional improvement with one point or more on the modified Rankin scale (compared to baseline).;Timepoint(s) of evaluation of this end point: 12 weeks after first dose of natalizumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include neurological improvement defined as a positive score (>0) in the EFIT overall evaluation and improvement on the AMC linear disability scale, Barthel index and PNS neurological scale after three natalizumab infusions compared to baseline Translational endpoints are: a) detection of HuD-specific T-lymphocytes in blood and CSF; b) phenotype of CSF cells (prior and after natalizumab) including B cells, T cells and DC; c) anti-HuD titers in CSF and serum; and d) single cell PCR on CSF derived plasma cells prior to treatment in order to determine the primary protein sequence of anti-HuD IgG ;Timepoint(s) of evaluation of this end point: Secondary endpoints: 12 weeks after first dose of natalizumab Translational endpoints: before (t=0) and 12 weeks after first dose of natalizumab | — |
Countries
Netherlands
Contacts
Public ContactSecretariaat Neurologie
Erasmus University Medical Center
Outcome results
None listed