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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Drug | Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival | 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. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse-Free Survival | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Burt, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University, Feinberg School of Medicine | Chicago | Illinois | 60611 | United States | ||
| Northwestern University |
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| ID | Term |
|---|---|
| D009471 | Neuromyelitis Optica |
| ID | Term |
|---|---|
| D009188 | Myelitis, Transverse |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D003520 | Cyclophosphamide |
| D015080 | Mesna |
| C512542 | thymoglobulin |
| D000961 | Antilymphocyte Serum |
| D008775 | Methylprednisolone |
| D008776 | Methylprednisolone Hemisuccinate |
| D000077555 | Methylprednisolone Acetate |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D000069585 | Filgrastim |
| D016756 | Immunoglobulins, Intravenous |
| D007074 | Immunoglobulin G |
| C495669 | Octagam |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Cyclophosphamide | Drug | A medication used as chemotherapy and to suppress the immune system |
|
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| Mesna | Drug | A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder |
|
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| rATG | Drug | A rabbit polyclonal antibody to lymphocytes |
|
|
| Methylprednisolone | Drug | A corticosteroid medication used to suppress the immune system and decrease inflammation |
|
|
| G-CSF | Drug | A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream |
|
|
| IVIg | Biological | Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects |
|
|
| Autologous Stem Cells | Biological | Infusion of patient's own stem cells |
|
| 5 years |
| Expanded Disability Status Scale (EDSS) Improvement | 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 | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Scripps Neurological Rating Scale (NRS) Improvement | The NRS scale ranges from 0 to 100 in 1 point increments that represent lower levels of disability. | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Improvement in Quality of Life | Measured using the short form (SF)-36 health survey. | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Paced Auditory Serial Addition Test (PASAT) Improvement | 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 | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Ambulation Index Improvement | 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. | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| 9 Hole Peg Test (9-HPT) Improvement | 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. | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Change in NMO IgG (aquaporin-4) Antibody Titer | Evaluation of the antibody titer, looking for a change from positive to negative. | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Improvement in Visual Acuity | 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. | 6 months, 1 year, 2 years, 3 years, 4 years, 5 years |
| Chicago |
| Illinois |
| 60611 |
| United States |
| D009902 | Optic Neuritis |
| D009901 | Optic Nerve Diseases |
| D003389 | Cranial Nerve Diseases |
| D003711 | Demyelinating Diseases |
| D005128 | Eye Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D007106 | Immune Sera |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D007132 | Immunoglobulin Isotypes |