Autologous Transplant To End NMO Spectrum Disorder

NCT03829566 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: DIAD.ATTEND.2018
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Neuromyelitis Optica; Devic's Disease; NMO Spectrum Disorder

Keywords

Autologous Stem Cell Transplantation; Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (9)

• Relapse-Free Survival

  5 years

• Expanded Disability Status Scale (EDSS) Improvement

  6 months, 1 year, 2 years, 3 years, 4 years, 5 years

• Scripps Neurological Rating Scale (NRS) Improvement

  6 months, 1 year, 2 years, 3 years, 4 years, 5 years

• Improvement in Quality of Life

  6 months, 1 year, 2 years, 3 years, 4 years, 5 years

• Paced Auditory Serial Addition Test (PASAT) Improvement

  6 months, 1 year, 2 years, 3 years, 4 years, 5 years

Study Arms (1)

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.

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

Interventions

Rituximab DRUG

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

Also known as: Rituxan

Hematopoietic Stem Cell Transplantation

Cyclophosphamide DRUG

A medication used as chemotherapy and to suppress the immune system

Also known as: Cytoxan

Hematopoietic Stem Cell Transplantation

Mesna DRUG

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

Also known as: Mesnex

Hematopoietic Stem Cell Transplantation

rATG DRUG

A rabbit polyclonal antibody to lymphocytes

Also known as: Thymoglobulin, Anti-Thymocyte Globulin

Hematopoietic Stem Cell Transplantation

Methylprednisolone DRUG

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

Also known as: Solu-Medrol, Depo-Medrol

Hematopoietic Stem Cell Transplantation

G-CSF DRUG

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

Also known as: Neupogen, Filgrastim, Granix, Zarxio

Hematopoietic Stem Cell Transplantation

IVIg BIOLOGICAL

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

Also known as: Bivigam, Carimune Nanofiltered (NF), Gammagard, Privigen, Octagam

Hematopoietic Stem Cell Transplantation

Autologous Stem Cells BIOLOGICAL

Infusion of patient's own stem cells

Hematopoietic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 - 65 years old at the time of pre-transplant evaluation
• An established diagnosis of NMOSD (with or without aquaporin 4 (AQP4)-IgG antibody)

You may not qualify if:

• Under age of 18 or over age of 65
• Prisoners
• 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).
• Paraplegia or quadriplegia (must be able to use a walker if even for only a few feet)
• Extensive subcortical white matter lesions
• 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
• Myocardial infarction within the last 12 months. If longer than 12 months, must pass a dobutamine stress test and be cleared by cardiology.
• Active systemic lupus erythematous, Sjogren's, myasthenia gravis, or another autoimmune disease
• Sickle cell disease, sickle cell disease, or coagulopathy
• Prior history of malignancy that required any radiotherapy, chemotherapy, or biological therapy
• 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
• Women who are breastfeeding
• Untreated life-threatening cardiac arrhythmia on electrocardiogram (EKG) or 24-hour holter
• Left ventricular ejection fraction (LVEF) \<50%
• 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

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (2)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

Rituximab; Cyclophosphamide; Mesna; thymoglobulin; Antilymphocyte Serum; Methylprednisolone; Methylprednisolone Hemisuccinate; Methylprednisolone Acetate; Granulocyte Colony-Stimulating Factor; Filgrastim; Immunoglobulins, Intravenous; Immunoglobulin G; Octagam

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Immune Sera; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Immunoglobulin Isotypes

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: February 4, 2019
• Study Start: November 1, 2019
• Primary Completion: January 1, 2025
• Study Completion: November 28, 2025
• Last Updated: November 20, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)