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Trial record 2 of 3 for:    "Neuromyelitis Optica Spectrum Disorder" | "Cyclophosphamide"

Autologous Transplant To End NMO Spectrum Disorder (ATTEND)

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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

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.

Condition or disease Intervention/treatment Phase
Neuromyelitis Optica Devic's Disease NMO Spectrum Disorder Drug: Rituximab Drug: Cyclophosphamide Drug: Mesna Drug: rATG Drug: Methylprednisolone Drug: G-CSF Biological: IVIg Biological: Autologous Stem Cells Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2026


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829566


Contacts
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Contact: Kathleen Quigley, RN 312-695-8192 kathleen.quigley@nm.org

Locations
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United States, Illinois
Northwestern University, Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Kathleen Quigley    312-695-4960    k-quigley@northwestern.edu   
Principal Investigator: Richard Burt, MD         
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Kathleen Quigley, RN    312-695-8192    kathleen.quigley@nm.org   
Principal Investigator: Richard Burt, MD         
Sponsors and Collaborators
Northwestern University
Investigators
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Principal Investigator: Richard Burt, MD Northwestern University

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Responsible Party: Richard Burt, MD, Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT03829566     History of Changes
Other Study ID Numbers: DIAD.ATTEND.2018
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Richard Burt, MD, Northwestern University:
Autologous Stem Cell Transplantation
Hematopoietic Stem Cell Transplant
Additional relevant MeSH terms:
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Neuromyelitis Optica
Cyclophosphamide
Disease
Pathologic Processes
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
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Rituximab
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action