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Autologous Transplant To End NMO Spectrum Disorder (ATTEND)

Primary Purpose

Neuromyelitis Optica, Devic's Disease, NMO Spectrum Disorder

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Rituximab

Cyclophosphamide

Mesna

rATG

Methylprednisolone

G-CSF

IVIg

Autologous Stem Cells

About this trial

This is an interventional treatment trial for Neuromyelitis Optica focused on measuring Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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
Serum creatinine >2.0 mg/dl
Liver cirrhosis, transaminases >2x of normal limits, or bilirubin >2.0 mg/dl unless due to Gilbert's disease
Major hematological abnormalities such as platelet count < 100,000/μl or absolute neutrophil count (ANC) < 1000/μl
Active infection except asymptomatic bacteriuria
Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have magnetic resonance imaging (MRI) exams
Known hypersensitivity to mouse, rabbit, or E. coli derived proteins
Human immunodeficiency virus (HIV) positive
Hepatitis B or C positive
Use of natalizumab (Tysabri) within the previous six months
Use of fingolimod (Gilenya) within the previous three months
Use of dimethyl fumarate (Tecfidera) within the previous three months
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
Use of alemtuzumab (Lemtrada/Campath) within previous 12 months
Use of rituximab (Rituxan) or ocrelizumab (Ocrevus) within previous six months
Prior treatment with mitoxantrone (Novantrone)

Sites / Locations

Northwestern University, Feinberg School of Medicine
Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hematopoietic Stem Cell Transplantation

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

Scripps Neurological Rating Scale (NRS) Improvement

The NRS scale ranges from 0 to 100 in 1 point increments that represent lower levels of disability.

Improvement in Quality of Life

Measured using the short form (SF)-36 health survey.

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

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.

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.

Change in NMO IgG (aquaporin-4) Antibody Titer

Evaluation of the antibody titer, looking for a change from positive to negative.

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.

Full Information

NCT ID

NCT03829566

First Posted

February 1, 2019

Last Updated

November 18, 2019

Sponsor

Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT03829566

Brief Title

Autologous Transplant To End NMO Spectrum Disorder

Acronym

ATTEND

Official Title

Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Withdrawn

Why Stopped

Discontinued by Investigator

Study Start Date

November 2019 (Anticipated)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

November 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuromyelitis Optica, Devic's Disease, NMO Spectrum Disorder

Keywords

Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hematopoietic Stem Cell Transplantation

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

A medication used as chemotherapy and to suppress the immune system

Intervention Type

Drug

Intervention Name(s)

Mesna

Other Intervention Name(s)

Mesnex

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

rATG

Other Intervention Name(s)

Thymoglobulin, Anti-Thymocyte Globulin

Intervention Description

A rabbit polyclonal antibody to lymphocytes

Intervention Type

Drug

Intervention Name(s)

Methylprednisolone

Other Intervention Name(s)

Solu-Medrol, Depo-Medrol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

G-CSF

Other Intervention Name(s)

Neupogen, Filgrastim, Granix, Zarxio

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

IVIg

Other Intervention Name(s)

Bivigam, Carimune Nanofiltered (NF), Gammagard, Privigen, Octagam

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Autologous Stem Cells

Intervention Description

Infusion of patient's own stem cells

Primary Outcome Measure Information:

Title

Progression-Free Survival

Description

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Relapse-Free Survival

Description

Time Frame

5 years

Title

Expanded Disability Status Scale (EDSS) Improvement

Description

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

Time Frame