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Autologous Transplant To End NMO Spectrum Disorder (ATTEND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03829566
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : July 25, 2019
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University

Tracking Information
First Submitted Date  ICMJE February 1, 2019
First Posted Date  ICMJE February 4, 2019
Last Update Posted Date July 25, 2019
Estimated Study Start Date  ICMJE November 2019
Estimated Primary Completion Date January 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
Progression-Free Survival [ Time Frame: 5 years ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
Progression-Free Survival [ Time Frame: 5 years ]
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.
Change History Complete list of historical versions of study NCT03829566 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Relapse-Free Survival [ Time Frame: 5 years ]
    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 [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    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 [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    The NRS scale ranges from 0 to 100 in 1 point increments that represent lower levels of disability.
  • Improvement in Quality of Life [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    Measured using the short form (SF)-36 health survey.
  • Paced Auditory Serial Addition Test (PASAT) Improvement [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    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 [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    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 [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    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 [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    Evaluation of the antibody titer, looking for a change from positive to negative.
  • Improvement in Visual Acuity [ Time Frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Transplant To End NMO Spectrum Disorder
Official Title  ICMJE Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuromyelitis Optica
  • Devic's Disease
  • NMO Spectrum Disorder
Intervention  ICMJE
  • Drug: Rituximab
    Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer
    Other Name: Rituxan
  • Drug: Cyclophosphamide
    A medication used as chemotherapy and to suppress the immune system
    Other Name: Cytoxan
  • Drug: Mesna
    A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
    Other Name: Mesnex
  • Drug: rATG
    A rabbit polyclonal antibody to lymphocytes
    Other Names:
    • Thymoglobulin
    • Anti-Thymocyte Globulin
  • Drug: Methylprednisolone
    A corticosteroid medication used to suppress the immune system and decrease inflammation
    Other Names:
    • Solu-Medrol
    • Depo-Medrol
  • Drug: G-CSF
    A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
    Other Names:
    • Neupogen
    • Filgrastim
    • Granix
    • Zarxio
  • Biological: IVIg
    Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects
    Other Names:
    • Bivigam
    • Carimune Nanofiltered (NF)
    • Gammagard
    • Privigen
    • Octagam
  • Biological: Autologous Stem Cells
    Infusion of patient's own stem cells
Study Arms  ICMJE Experimental: 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.
Interventions:
  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: Mesna
  • Drug: rATG
  • Drug: Methylprednisolone
  • Drug: G-CSF
  • Biological: IVIg
  • Biological: Autologous Stem Cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 1, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2026
Estimated Primary Completion Date January 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kathleen Quigley, RN 312-695-8192 kathleen.quigley@nm.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03829566
Other Study ID Numbers  ICMJE DIAD.ATTEND.2018
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Richard Burt, MD, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard Burt, MD Northwestern University
PRS Account Northwestern University
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP