Neuromyelitis Optica, Devic's Disease, NMO Spectrum Disorder
Conditions
Keywords
Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant
Brief summary
This study is designed to treat your disease with an autologous stem cell transplant using a regimen of immune suppressant drugs and chemotherapy to reset your immune system and to determine if your disease will go into long-term remission.
Detailed description
The autologous stem cell transplant used in this research study is an investigational procedure that uses cyclophosphamide (chemotherapy), rabbit antithymocyte globulin (rATG) (a protein that kills the immune cells that are thought to be causing your disease), rituximab (a biologic drug that targets B cells of your immune system), and intravenous immunoglobulin (IVIg) (pooled IgG antibodies from plasma donors with immunomodulatory and anti-inflammatory effects), followed by return of your own previously collected blood stem cells (autologous stem cell transplant). One day of plasmapheresis will also be performed the day prior to admission for stem cell transplant to remove disease-causing antibodies. The ability of this experimental treatment to stop relapses and progression (worsening) of your NMOSD will be assessed.
Interventions
DRUGRituximab
Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer
DRUGCyclophosphamide
A medication used as chemotherapy and to suppress the immune system
DRUGMesna
A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
DRUGrATG
A rabbit polyclonal antibody to lymphocytes
DRUGMethylprednisolone
A corticosteroid medication used to suppress the immune system and decrease inflammation
DRUGG-CSF
A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
BIOLOGICALIVIg
Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects
BIOLOGICALAutologous Stem Cells
Infusion of patient's own stem cells
Sponsors
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 - 65 years old at the time of pre-transplant evaluation 2. An established diagnosis of NMOSD (with or without aquaporin 4 (AQP4)-IgG antibody)
Exclusion criteria
1. Under age of 18 or over age of 65 2. Prisoners 3. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible, or any adult who is unable to consent (for adults cognitively impaired due to disease, consent may be obtained from the closest living relative). 4. Paraplegia or quadriplegia (must be able to use a walker if even for only a few feet) 5. Extensive subcortical white matter lesions 6. Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment 7. Myocardial infarction within the last 12 months. If longer than 12 months, must pass a dobutamine stress test and be cleared by cardiology. 8. Active systemic lupus erythematous, Sjogren's, myasthenia gravis, or another autoimmune disease 9. Sickle cell disease, sickle cell disease, or coagulopathy 10. Prior history of malignancy that required any radiotherapy, chemotherapy, or biological therapy 11. Positive pregnancy test, inability or unable to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy 12. Women who are breastfeeding 13. Untreated life-threatening cardiac arrhythmia on electrocardiogram (EKG) or 24-hour holter 14. Left ventricular ejection fraction (LVEF) \<50% 15. Tiffeneau-Pinelli index (FEV1/FVC) \<70% of predicted after bronchodilator therapy (if necessary), or diffusing capacity of lung for carbon monoxide (DLCO) hemoglobin corrected \<70 % predicted 16. Serum creatinine \>2.0 mg/dl 17. Liver cirrhosis, transaminases \>2x of normal limits, or bilirubin \>2.0 mg/dl unless due to Gilbert's disease 18. Major hematological abnormalities such as platelet count \< 100,000/μl or absolute neutrophil count (ANC) \< 1000/μl 19. Active infection except asymptomatic bacteriuria 20. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have magnetic resonance imaging (MRI) exams 21. Known hypersensitivity to mouse, rabbit, or E. coli derived proteins 22. Human immunodeficiency virus (HIV) positive 23. Hepatitis B or C positive 24. Use of natalizumab (Tysabri) within the previous six months 25. Use of fingolimod (Gilenya) within the previous three months 26. Use of dimethyl fumarate (Tecfidera) within the previous three months 27. Use of teriflunomide (Aubagio) unless cleared from the body (plasma concentration \<0.02mcg/ml) following elimination from the body with cholestyramine 8g three times a day for 11 days 28. Use of alemtuzumab (Lemtrada/Campath) within previous 12 months 29. Use of rituximab (Rituxan) or ocrelizumab (Ocrevus) within previous six months 30. Prior treatment with mitoxantrone (Novantrone)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | 5 years | Disease progression defined as: 1.0-point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least six months apart and not due to a non-NMO disease process. The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expanded Disability Status Scale (EDSS) Improvement | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability. Improvement in EDSS is defined by both a 0.5 or 1.0 points sustained for more than 6 months |
| Scripps Neurological Rating Scale (NRS) Improvement | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | The NRS scale ranges from 0 to 100 in 1 point increments that represent lower levels of disability. |
| Improvement in Quality of Life | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | Measured using the short form (SF)-36 health survey. |
| Paced Auditory Serial Addition Test (PASAT) Improvement | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Improvement measured with the 2 and 3 versions |
| Relapse-Free Survival | 5 years | Relapse defined as: Acute neurologic deterioration occurring after engraftment and lasting more than 24 hours, accompanied by objective worsening on neurological examination that are documented by a neurologist and not explained by fever, infection, stress, heat, drugs or related pseudo-exacerbation. Supportive confirmation by enhancement on MRI is preferred but not mandatory. |
| 9 Hole Peg Test (9-HPT) Improvement | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | The 9-HPT is a brief, standardized, quantitative test of upper extremity function. Both the dominant and non-dominant hands are tested twice, with the total time to complete the task each time recorded and then averaged. |
| Change in NMO IgG (aquaporin-4) Antibody Titer | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | Evaluation of the antibody titer, looking for a change from positive to negative. |
| Improvement in Visual Acuity | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | A visual acuity test is an eye exam that checks how well one sees the details of a letter or symbol from a specific distance. |
| Ambulation Index Improvement | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years | The subject's walk of 25 feet is timed and a score from 0 to 10 is assigned based on their walk/gait and/or assistance required. |
Countries
United States
Outcome results
None listed