Autologous Transplant To End NMO Spectrum Disorder (ATTEND)

Northwestern University

Status and phase: Withdrawn; Phase 3; Phase 2

Conditions: Devic's Disease; Neuromyelitis Optica; NMO Spectrum Disorder

Treatments: Drug: Cyclophosphamide; Drug: rATG; Drug: G-CSF; Biological: IVIg; Drug: Mesna; Biological: Autologous Stem Cells; Drug: Methylprednisolone; Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT03829566

DIAD.ATTEND.2018

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Hematopoietic Stem Cell Transplantation

Experimental group

Description:

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.

Treatment:

Biological: Autologous Stem Cells

Drug: Rituximab

Drug: Methylprednisolone

Drug: Mesna

Biological: IVIg

Drug: G-CSF

Drug: rATG

Drug: Cyclophosphamide