Clinical trial NCT03829566: Autologous Transplant To End NMO Spectrum Disorder
Official title: Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Neuromyelitis Optica
Devic's Disease
NMO Spectrum Disorder
Keywords: Autologous Stem Cell Transplantation
Hematopoietic Stem Cell Transplant
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2019-02-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression-Free Survival
timeFrame: 5 years
Secondary outcomes:
measure: Relapse-Free Survival
timeFrame: 5 years
measure: Expanded Disability Status Scale (EDSS) Improvement
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Scripps Neurological Rating Scale (NRS) Improvement
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Improvement in Quality of Life
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Paced Auditory Serial Addition Test (PASAT) Improvement
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Ambulation Index Improvement
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: 9 Hole Peg Test (9-HPT) Improvement
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Change in NMO IgG (aquaporin-4) Antibody Titer
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Improvement in Visual Acuity
timeFrame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University, Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Richard Burt, MD
role: PRINCIPAL_INVESTIGATOR
References: