Autologous Transplant To End NMO Spectrum Disorder

NCT ID: NCT03829566

Last Updated: 2019-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2/PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-30

Study Completion Date

2025-11-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Neuromyelitis Optica Devic's Disease NMO Spectrum Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hematopoietic Stem Cell Transplantation

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.

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer

Cyclophosphamide

Intervention Type DRUG

A medication used as chemotherapy and to suppress the immune system

Mesna

Intervention Type DRUG

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

rATG

Intervention Type DRUG

A rabbit polyclonal antibody to lymphocytes

Methylprednisolone

Intervention Type DRUG

A corticosteroid medication used to suppress the immune system and decrease inflammation

G-CSF

Intervention Type DRUG

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

IVIg

Intervention Type BIOLOGICAL

Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects

Autologous Stem Cells

Intervention Type BIOLOGICAL

Infusion of patient's own stem cells

Interventions

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Rituximab

Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer

Intervention Type DRUG

Cyclophosphamide

A medication used as chemotherapy and to suppress the immune system

Intervention Type DRUG

Mesna

A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder

Intervention Type DRUG

rATG

A rabbit polyclonal antibody to lymphocytes

Intervention Type DRUG

Methylprednisolone

A corticosteroid medication used to suppress the immune system and decrease inflammation

Intervention Type DRUG

G-CSF

A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Intervention Type DRUG

IVIg

Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects

Intervention Type BIOLOGICAL

Autologous Stem Cells

Infusion of patient's own stem cells

Intervention Type BIOLOGICAL

Other Intervention Names

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Rituxan Cytoxan Mesnex Thymoglobulin Anti-Thymocyte Globulin Solu-Medrol Depo-Medrol Neupogen Filgrastim Granix Zarxio Bivigam Carimune Nanofiltered (NF) Gammagard Privigen Octagam

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northwestern University

OTHER

Sponsor Role lead

Responsible Party

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Richard Burt, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Richard Burt, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

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Northwestern University, Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Countries

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United States

Other Identifiers

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DIAD.ATTEND.2018

Identifier Type: -

Identifier Source: org_study_id

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