Autologous Transplant To End NMO Spectrum Disorder

Neuromyelitis Optica Clinical Trial

— ATTEND  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03829566
• Other study ID #: DIAD.ATTEND.2018
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: November 2019
• Est. completion date: November 28, 2025

Study information

• Verified date: November 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 28, 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Devic's Disease
• Disease
• Neuromyelitis Optica
• NMO Spectrum Disorder

Intervention

Drug:
• Rituximab
Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer
• Cyclophosphamide
A medication used as chemotherapy and to suppress the immune system
• Mesna
A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
• rATG
A rabbit polyclonal antibody to lymphocytes
• Methylprednisolone
A corticosteroid medication used to suppress the immune system and decrease inflammation
• G-CSF
A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Biological:
• IVIg
Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects
• Autologous Stem Cells
Infusion of patient's own stem cells

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	Northwestern University, Feinberg School of Medicine	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	5 years
Secondary	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	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Scripps Neurological Rating Scale (NRS) Improvement	The NRS scale ranges from 0 to 100 in 1 point increments that represent lower levels of disability.	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Improvement in Quality of Life	Measured using the short form (SF)-36 health survey.	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	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	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	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.	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	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.	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	Change in NMO IgG (aquaporin-4) Antibody Titer	Evaluation of the antibody titer, looking for a change from positive to negative.	6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary	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.	6 months, 1 year, 2 years, 3 years, 4 years, 5 years