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Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) (BEAT-MS)

Primary Purpose

Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Autologous Hematopoietic Stem Cell Transplantation
Best Available Therapy (BAT)
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Multiple Sclerosis focused on measuring Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant(s) must meet all of the following criteria to be eligible for this study:

  1. Diagnosis of Multiple Sclerosis (MS) according to the 2017 McDonald Criteria
  2. (Kurtzke) Expanded Disability Status Scale (EDSS) ≤ 6.0 at the time of randomization (Day 0)
  3. T2 abnormalities on brain Magnetic Resonance Imaging (MRI) that fulfill the 2017 McDonald MRI criteria for dissemination in space

    --A detailed MRI report or MRI images must be available for review by the site neurology investigator.

  4. Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria as described below:

    1. At least one episode of disease activity must occur following ≥ 1 month of treatment with an oral DMT approved by the FDA or MHRA for the treatment of relapsing MS, or a monoclonal antibody, specifically: dimethyl fumarate (Tecfidera®), diroximel fumarate, teriflunomide (Aubagio®), cladribine (Mavenclad®), daclizumab (Zinbryta®), siponimod (Mayzent®), ozanimod, fingolimod (Gilenya®), rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), or ofatumumab (Arzerra®), and
    2. At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and
    3. At least one episode of disease activity must be a clinical MS relapse (see item c.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical

    MS relapse or MRI evidence of disease activity (see item d.ii. below):

    i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee, and

    ii. MRI evidence of disease activity must include ≥ 2 unique active lesions on a brain or spinal cord MRI. A detailed MRI report or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following:

    • A gadolinium-enhancing lesion, or
    • A new non-enhancing T2 lesion compared to a reference scan obtained not more than 24 months prior to the screening visit (Visit -2).
  5. Candidacy for treatment with at least one of the following high efficacy DMTs:

    Cladribine, natalizumab, alemtuzumab, ocrelizumab, rituximab, and ofatumumab (after approval by the FDA for relapsing MS). Candidacy for treatment for each DMT is defined as meeting all of the following:

    • No prior disease activity with the candidate DMT, and
    • No contraindication to the candidate DMT, and
    • No treatment with the candidate DMT in the 12 months prior to screening.
  6. Completion of SARS-CoV-2 vaccination series ≥ 14 days prior to randomization (Day 0).
  7. Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0).
  8. Insurance or public funding approval for MS treatment with at least one candidate DMT, and
  9. Ability to comply with study procedures and provide informed consent, in the opinion of the investigator.

Exclusion Criteria:

Subject(s) who meet any of the following criteria will not be eligible for this study:

  1. Diagnosis of primary progressive Multiple Sclerosis (MS) according to the 2017 McDonald criteria
  2. History of neuromyelitis optica or anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies associated encephalomyelitis
  3. Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer. Agents authorized by the FDA or MHRA for prevention or treatment of SARS-CoV-2 are not considered investigational.
  4. Either of the following within one month prior to randomization (Day 0):

    1. Onset of acute MS relapse, or
    2. Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
  5. Initiation of natalizumab, alemtuzumab, ocrelizumab, or rituximab between screening visit (Visit -2) and randomization (Day 0)
  6. Brain MRI or Cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML)
  7. History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)
  8. Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis
  9. History of sickle cell anemia or other hemoglobinopathy
  10. Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C

    -Note: Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.

  11. Presence or history of mild to severe cirrhosis
  12. Hepatic disease with the presence of either of the following:

    1. Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin

      • 3.0 times the ULN in the presence of Gilbert's syndrome, or
    2. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
  13. Positive SARS-CoV-2 PCR test, or alternative nucleic acid amplification test (NAAT) per institutional standards, within 14 days prior to randomization (Day 0).
  14. Evidence of HIV infection
  15. Positive QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test results (e.g., blood test results. Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test results.
  16. Active viral, bacterial, endoparasitic, or opportunistic infections
  17. Active invasive fungal infection
  18. Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist
  19. Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0)
  20. Presence or history of clinically significant cardiac disease including:

    1. Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions
    2. Coronary artery disease with a documented diagnosis of either:

      • Chronic exertional angina, or
      • Signs or symptoms of congestive heart failure.
    3. Evidence of heart valve disease, including any of the following:

      • Moderate to severe valve stenosis or insufficiency,
      • Symptomatic mitral valve prolapse, or
      • Presence of prosthetic mitral or aortic valve.
  21. Left ventricular ejection fraction (LVEF) < 50%
  22. Impaired renal function defined as Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  23. Forced expiratory volume in one second (FEV1) <70% predicted (no bronchodilator)
  24. Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) < 70% predicted
  25. Poorly controlled diabetes mellitus, defined as HbA1c >8%
  26. History of malignancy, with the exception of adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix.

    -Note:Malignancies for which the participant is judged to be cured prior to randomization (Day 0) will be considered on an individual basis by the study adjudication committee.

  27. Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following:

    • systemic lupus erythematous
    • systemic sclerosis
    • rheumatoid arthritis
    • Sjögren's syndrome
    • polymyositis
    • dermatomyositis
    • mixed connective tissue disease
    • polymyalgia rheumatica
    • polychondritis
    • sarcoidosis
    • vasculitis syndromes, or
    • unspecified collagen vascular disease.
  28. Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer
  29. Prior history of AHSCT
  30. Prior history of solid organ transplantation
  31. Positive pregnancy test or breast-feeding
  32. Inability or unwillingness to use effective means of birth control
  33. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
  34. Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent
  35. History of hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins
  36. Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with gadolinium administration
  37. Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage
  38. Presence or history of other neurological disorders, including but not limited to:

    • central nervous system (CNS) or spinal cord tumor
    • metabolic or infectious cause of myelopathy
    • genetically-inherited progressive CNS disorder
    • CNS sarcoidosis, or
    • systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
  39. Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality, or
  40. Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.

Sites / Locations

  • Stanford Multiple Sclerosis CenterRecruiting
  • Rocky Mountain Multiple Sclerosis Center, University of Colorado School of MedicineRecruiting
  • University of Massachusetts Memorial Medical CenterRecruiting
  • University of Minnesota Multiple Sclerosis CenterRecruiting
  • Mayo ClinicRecruiting
  • John L. Trotter Multiple Sclerosis Center, Washington University School of Medicine in St. LouisRecruiting
  • Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount SiinaiRecruiting
  • Rochester Multiple Sclerosis Center, University of Rochester
  • Duke University Medical CenterRecruiting
  • University of Cincinnati (UC) Waddell Center for Multiple SclerosisRecruiting
  • Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland ClinicRecruiting
  • Multiple Sclerosis Center, Oregon Health & Science UniversityRecruiting
  • Penn Comprehensive MS Center, Hospital of the University of PennsylvaniaRecruiting
  • University of Texas Southwestern Medical Center: Division of Multiple Sclerosis and NeuroimmunologyRecruiting
  • Maxine Mesigner Multiple Sclerosis Comprehensive Care Center, Baylor College of Medicine Medical CenterRecruiting
  • Virginia Commonwealth University Multiple Sclerosis Treatment and Research CenterRecruiting
  • Clinical Research Division, Fred Hutchinson Cancer Research CenterRecruiting
  • Multiple Sclerosis Center, Swedish Neuroscience InstituteRecruiting
  • Multiple Sclerosis Center at Northwest HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

AHSCT

Best Available Therapy (BAT)

Arm Description

AHSCT: Myeloablative and Immunoablative therapy followed by Autologous Hematopoietic Stem Cell Transplantation Participants will undergo: Mobilization and graft collection: mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide, filgrastim, and dexamethasone. The autologous graft will be collected by leukapheresis and cryopreserved. Conditioning: high dose myeloablative and immunoablative conditioning with a six-day BEAM chemotherapy and rabbit anti-thymocyte globulin regimen will be initiated ≥30 days after cyclophosphamide mobilization. Autologous cryopreserved graft infusion: the cryopreserved peripheral blood stem cells (PBSC) graft will be thawed and infused the day following completion of the conditioning regimen. Each bag will be thawed and infused according to institutional standards consistent with the Foundation for the Accreditation of Cellular Therapy (FACT) guidelines. Participants will receive prednisone following graft infusion.

Participants randomized to BAT: Best available therapy will be selected by the Site Investigator from: Cladribine (Mavenclad®), natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), ocrelizumab (Ocrevus®), ublituximab (BRIUMVI™), rituximab (Rituxan®), or ofatumumab (Arzerra®) (after approval by the FDA for relapsing MS).

Outcomes

Primary Outcome Measures

Multiple Sclerosis (MS) Relapse-Free Survival
MS relapse-free survival, analyzed as time from treatment randomization until MS relapse or death from any cause.

Secondary Outcome Measures

Number of Multiple Sclerosis (MS) Relapses Per Year
Annual Relapse Rate (ARR) time calculated as number of confirmed relapses divided by time in study per year.
The Occurrence of Any Evidence of Multiple Sclerosis (MS) Disease Activity or Death From Any Cause
The occurrence of any evidence of MS disease activity or death from any cause, analyzed as time-to-event.
The Occurence of Confirmed Disability Worsening by the Kurtz Expanded Disability Status Scale (EDSS)
Measured by the Kurtzke Expanded Disability Status Scale performed by the masked (blinded) rater. EDSS, defined by: A decrease in EDSS of ≥ 1.0 step(s) compared to the EDSS at randomization (Day 0) and Confirmation of disability improvement ≥ 6 months later. The time of confirmed disability worsening measured by EDSS will be the time of first increase in EDSS ≥ 1.0 step(s).
The Occurrence of Confirmed Disability Improvement by the Kurtz Expanded Disability Status Scale (EDSS)
Measured by the Kurtzke Expanded Disability Status Scale performed by the masked (blinded) rater. Confirmed disability improvement defined by: A decrease in EDSS of ≥ 1.0 step(s) compared to the EDSS at randomization (Day 0) and Confirmation of disability improvement ≥ 6 months later. The time of confirmed disability improvement measured by EDSS will be the time of first decrease in EDSS ≥ 1.0 step(s).
Whole Brain Volume Change from Pre-Randomization Visit to the follow-up evaluations
Method of assessment: Magnetic Resonance Imaging (MRI) imaging.
Change in Serum Neurofilament Light Chain (NfL) Concentration
Extent of neurofilament light chain (NfL) concentration in serum is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid and subsequently blood following neuro-axonal damage.
The Occurrence of Death From Any Cause: All-Cause Mortality
Any death, regardless of relationship to treatment.
Proportion of Participants who Experience a Serious Adverse Event (SAE)
An event that results in any of the following outcomes: Death, A life-threatening event that places the participant at immediate risk of death, Inpatient hospitalization or prolongation of existing hospitalization, Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or A congenital anomaly or birth defect. Note: Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Reference: Code of Federal Regulations Title 21 Part 312.32(a)
Proportion of Participants with a Grade 3 or Higher Infection
In accordance with the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events NCI-CTCAE version 5.0, published November 27, 2017.
Proportion of Participants with Progressive Multifocal Leukoencephalopathy (PML)
The occurrence of PML during the course of participation in this study. A disease of the white matter of the brain, caused by a virus infection, Polyomavirus JC (JC virus), that targets cells that make myelin--the material that insulates nerve cells (neurons).
Time to Neutrophil Engraftment Among Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients
Neutrophil engraftment is defined as absolute neutrophil count (ANC) > 500/µl on two consecutive measurements on different days.
Proportion of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients Who Experience Primary or Secondary Graft Failure
Graft failure can either be primary (graft never established) or secondary (loss of an established graft). Primary graft failure is the absence of adequate hematopoiesis by Day T28, defined as meeting all of the following conditions: Bone marrow cellularity <5%, Peripheral White Blood Cell Count (WBC) < 500/µl, Peripheral Absolute Neutrophil Count (ANC) < 100/ µl, and Platelets < 10,000/ µl.

Full Information

First Posted
August 5, 2019
Last Updated
October 6, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), Blood and Marrow Transplant Clinical Trials Network, PPD, Rho Federal Systems Division, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04047628
Brief Title
Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS)
Acronym
BEAT-MS
Official Title
A Multicenter Randomized Controlled Trial of Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (ITN077AI)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2019 (Actual)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
October 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), Blood and Marrow Transplant Clinical Trials Network, PPD, Rho Federal Systems Division, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multi-center prospective rater-masked (blinded) randomized controlled trial of 156 participants, comparing the treatment strategy of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) to the treatment strategy of Best Available Therapy (BAT) for treatment-resistant relapsing multiple sclerosis (MS). Participants will be randomized at a 1 to 1 (1:1) ratio. All participants will be followed for 72 months after randomization (Day 0, Visit 0).
Detailed Description
Participant recruitment for this six-year research study focuses on multiple sclerosis (MS) that has remained active despite treatment. This study will compare high dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) to best available therapy (BAT) in the treatment of relapsing MS. MS is a disease caused by one's own immune cells. Normally, immune cells fight infection. In MS, immune cells called T cells, or chemical products made by immune cells, react against the covering or coat (myelin) of nerve fibers in the brain and spinal cord. This leads to stripping the coat from certain nerve fibers (demyelination), and this causes neurologic problems. MS can cause loss of vision, weakness or incoordination, loss or changes in sensation, problems with thinking or memory, problems controlling urination, and other disabilities. Most individuals with MS first have immune attacks (called relapses) followed by periods of stability. Over time, MS can have episodes of new and worsening symptoms, ranging from mild to disabling. This is called relapsing MS. Relapsing MS includes relapsing remitting MS (RRMS) and secondary progressive MS (SPMS). There are medicines (drugs) to decrease relapses, but these are neither considered to be curative nor, to induce prolonged remissions without continuing therapy. More than a dozen medicines have been approved for the treatment of relapsing forms of MS. These medicines differ in how safe they are and how well they work. Despite availability of an increasing number of effective medicines, some individuals with relapsing MS do not respond to treatment. Research is being conducted to find other treatments. High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) has been shown to help relapsing MS in cases where medicines did not work. AHSCT involves collecting stem cells, which are produced in the bone marrow. These stem cells are "mobilized" to leave the bone marrow and move into the blood where they can be collected and stored. Participants will then receive chemotherapy intended to kill immune cells. One's own stored (frozen) stem cells are then given back, through an infusion. This "transplant" of one's stem cells allows the body to form new immune cells in order to restore their immune system. New research suggest that MS might be better controlled with AHSCT than with medicines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Keywords
Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
156 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AHSCT
Arm Type
Experimental
Arm Description
AHSCT: Myeloablative and Immunoablative therapy followed by Autologous Hematopoietic Stem Cell Transplantation Participants will undergo: Mobilization and graft collection: mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide, filgrastim, and dexamethasone. The autologous graft will be collected by leukapheresis and cryopreserved. Conditioning: high dose myeloablative and immunoablative conditioning with a six-day BEAM chemotherapy and rabbit anti-thymocyte globulin regimen will be initiated ≥30 days after cyclophosphamide mobilization. Autologous cryopreserved graft infusion: the cryopreserved peripheral blood stem cells (PBSC) graft will be thawed and infused the day following completion of the conditioning regimen. Each bag will be thawed and infused according to institutional standards consistent with the Foundation for the Accreditation of Cellular Therapy (FACT) guidelines. Participants will receive prednisone following graft infusion.
Arm Title
Best Available Therapy (BAT)
Arm Type
Active Comparator
Arm Description
Participants randomized to BAT: Best available therapy will be selected by the Site Investigator from: Cladribine (Mavenclad®), natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), ocrelizumab (Ocrevus®), ublituximab (BRIUMVI™), rituximab (Rituxan®), or ofatumumab (Arzerra®) (after approval by the FDA for relapsing MS).
Intervention Type
Procedure
Intervention Name(s)
Autologous Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
AHSCT
Intervention Description
PBSC mobilization & collection regimen per protocol/ institutional standards includes: intravenous cyclophosphamide (Cytoxan®), 4 grams/m^2); intravenous mesna (Mesnex®),a total delivery of 4 grams/m^2); oral dexamethasone, 10 mg dose, four times daily); subcutaneous filgrastim,10 mcg/kg/day until leukapheresis goal is completed; and CD34+ peripheral blood stem cells collection by leukapheresis. Conditioning per protocol& institutional standards: 6-day BEAM (e.g. Carmustine (BCNU), Etoposide (VP-16), Cytarbine (Ara-C), and Melphalan) chemotherapy protocol and, rabbit anti-thymocyte globulin (rATG) 2.5 mg/kg/day x2 Autologous cryopreserved graft infusion: The target Cluster of Differentiation (CD)34+ cell dose for infusion is 5 x 10^6 CD34+ cells/kg (minimum 4 x 10^6 CD34+ cells/kg; maximum 7.5 x 10^6 CD34+ cells/kg). For 1&2 above: Ideal body weight (IBW) versus Actual Body Weight (ABW) are applicable.
Intervention Type
Biological
Intervention Name(s)
Best Available Therapy (BAT)
Other Intervention Name(s)
natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), ocrelizumab (Ocrevus®), rituximab (Rituxan®), cladribine (Mavenclad®), ofatumumab (Kesimpta®), ublituximab (BRIUMVI™)
Intervention Description
Disease-modifying therapy (DMT) selected by the Site Investigator from the below: cladribine natalizumab alemtuzumab ocrelizumab, rituximab, ofatumumab, or ublituximab
Primary Outcome Measure Information:
Title
Multiple Sclerosis (MS) Relapse-Free Survival
Description
MS relapse-free survival, analyzed as time from treatment randomization until MS relapse or death from any cause.
Time Frame
From Day 0 (Randomization to Treatment) Up to 36 Months (3 Years)
Secondary Outcome Measure Information:
Title
Number of Multiple Sclerosis (MS) Relapses Per Year
Description
Annual Relapse Rate (ARR) time calculated as number of confirmed relapses divided by time in study per year.
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
The Occurrence of Any Evidence of Multiple Sclerosis (MS) Disease Activity or Death From Any Cause
Description
The occurrence of any evidence of MS disease activity or death from any cause, analyzed as time-to-event.
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
The Occurence of Confirmed Disability Worsening by the Kurtz Expanded Disability Status Scale (EDSS)
Description
Measured by the Kurtzke Expanded Disability Status Scale performed by the masked (blinded) rater. EDSS, defined by: A decrease in EDSS of ≥ 1.0 step(s) compared to the EDSS at randomization (Day 0) and Confirmation of disability improvement ≥ 6 months later. The time of confirmed disability worsening measured by EDSS will be the time of first increase in EDSS ≥ 1.0 step(s).
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
The Occurrence of Confirmed Disability Improvement by the Kurtz Expanded Disability Status Scale (EDSS)
Description
Measured by the Kurtzke Expanded Disability Status Scale performed by the masked (blinded) rater. Confirmed disability improvement defined by: A decrease in EDSS of ≥ 1.0 step(s) compared to the EDSS at randomization (Day 0) and Confirmation of disability improvement ≥ 6 months later. The time of confirmed disability improvement measured by EDSS will be the time of first decrease in EDSS ≥ 1.0 step(s).
Time Frame
Day 0 (Randomization to Treatment) Up to Month 72 (6 Years)
Title
Whole Brain Volume Change from Pre-Randomization Visit to the follow-up evaluations
Description
Method of assessment: Magnetic Resonance Imaging (MRI) imaging.
Time Frame
From Visit Pre-R Up to 72 Months (6 Years)
Title
Change in Serum Neurofilament Light Chain (NfL) Concentration
Description
Extent of neurofilament light chain (NfL) concentration in serum is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid and subsequently blood following neuro-axonal damage.
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
The Occurrence of Death From Any Cause: All-Cause Mortality
Description
Any death, regardless of relationship to treatment.
Time Frame
Day 0 (Randomization to Treatment) Up to Month 72 (6 Years)
Title
Proportion of Participants who Experience a Serious Adverse Event (SAE)
Description
An event that results in any of the following outcomes: Death, A life-threatening event that places the participant at immediate risk of death, Inpatient hospitalization or prolongation of existing hospitalization, Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or A congenital anomaly or birth defect. Note: Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Reference: Code of Federal Regulations Title 21 Part 312.32(a)
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
Proportion of Participants with a Grade 3 or Higher Infection
Description
In accordance with the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events NCI-CTCAE version 5.0, published November 27, 2017.
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
Proportion of Participants with Progressive Multifocal Leukoencephalopathy (PML)
Description
The occurrence of PML during the course of participation in this study. A disease of the white matter of the brain, caused by a virus infection, Polyomavirus JC (JC virus), that targets cells that make myelin--the material that insulates nerve cells (neurons).
Time Frame
From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years)
Title
Time to Neutrophil Engraftment Among Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients
Description
Neutrophil engraftment is defined as absolute neutrophil count (ANC) > 500/µl on two consecutive measurements on different days.
Time Frame
From Day of Graft Infusion (Receipt of Peripheral Blood Stem Cells-PBSC Infusion) Up to 72 Months (6 Years)
Title
Proportion of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients Who Experience Primary or Secondary Graft Failure
Description
Graft failure can either be primary (graft never established) or secondary (loss of an established graft). Primary graft failure is the absence of adequate hematopoiesis by Day T28, defined as meeting all of the following conditions: Bone marrow cellularity <5%, Peripheral White Blood Cell Count (WBC) < 500/µl, Peripheral Absolute Neutrophil Count (ANC) < 100/ µl, and Platelets < 10,000/ µl.
Time Frame
From Day of Transplant (Receipt of Peripheral Blood Stem Cells-PBSC Infusion) Up to Day 28 Post Transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 to 55 years, inclusive, at the time of the screening Visit -2. Diagnosis of MS according to the 2017 McDonald Criteria139. EDSS ≤ 6.0 at the time of randomization (Day 0). T2 abnormalities on brain MRI that fulfill the 2017 McDonald MRI criteria for dissemination in space139. A detailed MRI report or MRI images must be available for review by the site neurology investigator. Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria described below: At least one episode of disease activity must occur following ≥ 1 month of treatment with one of the following: (i) an oral DMT approved by the FDA for the treatment of relapsing MS, or (ii) a monoclonal antibody approved by the FDA for the treatment of relapsing MS, or (iii) rituximab. Qualifying DMTs include: dimethyl fumarate, diroximel fumarate, monomethyl fumarate, teriflunomide, cladribine, daclizumab, ponesimod, siponimod, ozanimod, fingolimod, rituximab, ocrelizumab, natalizumab, alemtuzumab, ublituximab, and ofatumumab, and At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and At least one episode of disease activity must be a clinical MS relapse (see item c.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical MS relapse or MRI evidence of disease activity (see item c.ii. below): i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee (see Section 3.5), and ii. MRI evidence of disease activity must include ≥ 1 unique active lesion on one or more brain or spinal cord MRIs. Detailed MRI reports or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following: 1. A gadolinium-enhancing lesion, or 2. A new non-enhancing T2 lesion compared to a reference scan obtained not more than 36 months prior to the screening visit (Visit -2). 6. Candidacy for treatment with at least one of the following high efficacy BAT DMTs: cladribine, natalizumab, alemtuzumab, ocrelizumab, ofatumumab, ublituximab and rituximab. Candidacy for treatment for each BAT DMT is defined as meeting all of the following: No prior disease activity episode, as defined in Inclusion Criterion #5, with the candidate BAT DMT, and No contraindication to the candidate BAT DMT, and No treatment with the candidate BAT DMT in the 12 months prior to screening. 7. Completion of COVID-19 vaccination series, according to the current Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations, ≥ 14 days prior to randomization (Day 0). 8. Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0). 9. Insurance approval for MS treatment with at least one candidate BAT DMT (see Inclusion Criterion #6). 10. Ability to comply with study procedures and provide informed consent, in the opinion of the investigator. 11. Females of childbearing potential (defined in Section 5.4.3.1) and males with female partners of childbearing potential are required to adhere to the contraception provisions of Section 5.4.3.1. 12. For participants who use medicinal or recreational marijuana, willingness to substitute MARINOL® if randomized to AHSCT (Section 5.4.2.6). Exclusion Criteria: Diagnosis of primary progressive MS according to the 2017 McDonald criteria. History of neuromyelitis optica spectrum disorder or MOG antibody disease. Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of COVID-19 are not considered investigational. Either of the following within one month prior to randomization (Day 0): Onset of acute MS relapse, or Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent. Initiation of any BAT DMT (see Section 5.2.1) between Visit -2 and randomization (Day 0). Brain MRI or cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML). History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS). Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis. History of sickle cell anemia or other hemoglobinopathy. Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection. Presence or history of mild to severe cirrhosis. Hepatic disease with the presence of either of the following: Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin ≥ 3.0 times the ULN in the presence of Gilbert's syndrome, or Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN. Positive COVID-19 PCR test, or alternative nucleic acid amplification test (NAAT) per institutional standards, within 14 days prior to randomization (Day 0). Evidence of HIV infection. Positive QuantiFERON - TB Gold,TB Gold Plus, or T-SPOT®.TB test results. PPD tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test. Active viral, bacterial, endoparasitic, or opportunistic infections. Active invasive fungal infection. Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist. Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0). Presence or history of clinically significant cardiac disease including: a. Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions. b. Coronary artery disease with a documented diagnosis of either: i. Chronic exertional angina, or ii. Signs or symptoms of congestive heart failure. c. Evidence of heart valve disease, including any of the following: i. Moderate to severe valve stenosis or insufficiency, or ii. Symptomatic mitral valve prolapse, or iii. Presence of prosthetic mitral or aortic valve. Left ventricular ejection fraction (LVEF) < 50%. Impaired renal function defined as eGFR < 60 mL/min/1.73 m2, according to the CKD-EPI formula144. Forced expiratory volume in one second (FEV1) < 70% predicted (no bronchodilator). Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) < 70% predicted. Poorly controlled diabetes mellitus, defined as HbA1c > 8%. History of malignancy, except adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix. Malignancies for which the participant is judged to be cured will be considered on an individual basis by the study adjudication committee (see Section 3.5). Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following: systemic lupus erythematous, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, polymyositis, dermatomyositis, mixed connective tissue disease, polymyalgia rheumatica, polychondritis, sarcoidosis, vasculitis syndromes, or unspecified collagen vascular disease. Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer. Prior history of AHSCT. Prior history of solid organ transplantation. Positive pregnancy test or breastfeeding. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy. Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent. History of hypersensitivity to rabbit or Escherichia coli-derived proteins. Any metallic material or electronic device in the body, or other condition that precludes the participant from undergoing MRI with gadolinium administration, as determined by the site radiologist. Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage. Presence or history of other neurological disorders, including but not limited to CNS or spinal cord tumor; metabolic or infectious cause of myelopathy; genetically-inherited progressive CNS disorder; CNS sarcoidosis; or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments. Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality. Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey A. Cohen, MD
Organizational Affiliation
Mellen Center for MS Treatment and Research, Cleveland Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
George E. Georges, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Paolo A. Muraro, MD, PhD
Organizational Affiliation
Department of Medicine, Imperial College London
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford Multiple Sclerosis Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sujatha Kalle
Phone
650-319-5522
Email
skalle@stanford.edu
First Name & Middle Initial & Last Name & Degree
Jeffrey Dunn, MD, FAAN
Facility Name
Rocky Mountain Multiple Sclerosis Center, University of Colorado School of Medicine
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timber Bourassa, BS
Phone
303-724-8305
Email
NeurologyResearchPartners@cuanschutz.edu
First Name & Middle Initial & Last Name & Degree
John R. Corboy, MD
Facility Name
University of Massachusetts Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nimmy Kanichai Francis, PhD,MBBS
Phone
774-441-7695
Email
Nimmy.KanichaiFrancis@umassmed.edu
First Name & Middle Initial & Last Name & Degree
Carolina Ionete, MD, PhD
Facility Name
University of Minnesota Multiple Sclerosis Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Harper
Phone
651-333-0841
Email
harpe442@umn.edu
First Name & Middle Initial & Last Name & Degree
Adam Carpenter, MD
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina McCarthy
Phone
507-284-4423
Email
mccarthy.christina@mayo.edu
First Name & Middle Initial & Last Name & Degree
B. Mark Keegan, MD,FRCPC
Facility Name
John L. Trotter Multiple Sclerosis Center, Washington University School of Medicine in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Teeter
Phone
314-747-6247
Email
lteeter@wustl.edu
First Name & Middle Initial & Last Name & Degree
Gregory Wu, MD, PhD
Facility Name
Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Siinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Filomena
Phone
212-241-3841
Email
susan.e.filomena@mssm.edu
First Name & Middle Initial & Last Name & Degree
Aaron Miller, MD
Facility Name
Rochester Multiple Sclerosis Center, University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14620
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew D. Goodman, MD
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debbie Dahnke, NRC, RN
Phone
919-684-1590
Email
deborah.dahnke@duke.edu
First Name & Middle Initial & Last Name & Degree
Katherine Beck, CRC, RN, BSN
Phone
919-668-2278
Email
kate.beck@duke.edu
First Name & Middle Initial & Last Name & Degree
Suma Shah, MD
Facility Name
University of Cincinnati (UC) Waddell Center for Multiple Sclerosis
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tiffany Rupert, CCRC
Phone
513-558-0269
Email
BEATMSResearch@UCHealth.com
First Name & Middle Initial & Last Name & Degree
Aram Zabeti, MD
Facility Name
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Glazer
Phone
216-445-9855
Email
glazerm@ccf.org
First Name & Middle Initial & Last Name & Degree
Jeffrey A. Cohen, MD
Facility Name
Multiple Sclerosis Center, Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debbie Guess, RN
Phone
503-494-7651
Email
griffide@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Yadav Vijayshree, MD,MCR,FANA,FAAN
Facility Name
Penn Comprehensive MS Center, Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MS MS Clinical Research Team
Phone
215-906-4778
Email
msresearch@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Amit Bar-Or, MD,FRCP,FAAN,FANA
Facility Name
University of Texas Southwestern Medical Center: Division of Multiple Sclerosis and Neuroimmunology
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manual Huichapa
Phone
214-645-8216
Email
manuel.huichapa@utsoutwestern.edu
First Name & Middle Initial & Last Name & Degree
Benjamin Greenberg, MD
Facility Name
Maxine Mesigner Multiple Sclerosis Comprehensive Care Center, Baylor College of Medicine Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tahari Griffin
Phone
713-798-6097
Email
tgriffin@bcm.edu
First Name & Middle Initial & Last Name & Degree
George J. Hutton, MD
Facility Name
Virginia Commonwealth University Multiple Sclerosis Treatment and Research Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Unsong Oh, MD
Phone
804-828-3067
Email
unsong.oh@vcuhealth.org
First Name & Middle Initial & Last Name & Degree
Unsong Oh, MD
Facility Name
Clinical Research Division, Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernadette McLaughlin
Phone
206-667-4916
Email
bmclaugh@fredhutch.org
First Name & Middle Initial & Last Name & Degree
George E. Georges, MD
Facility Name
Multiple Sclerosis Center, Swedish Neuroscience Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernadette McLaughlin
Phone
206-667-4916
Email
bmclaugh@fredhutch.org
First Name & Middle Initial & Last Name & Degree
James D. Bowen, MD
Facility Name
Multiple Sclerosis Center at Northwest Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98133
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernadette McLaughlin
Phone
206-667-4916
Email
bmclaugh@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Annette Wundes, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Participant level data access and additional relevant materials will be made available upon completion of the trial.
IPD Sharing Time Frame
After completion of the trial, within 24 months status post database lock.
IPD Sharing Access Criteria
Registration is available for the Immunology Database and Analysis Portal (ImmPort) at: https://www.immport.org/registration and submit a rationale for the purpose of requesting study data access. ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.
IPD Sharing URL
https://www.immport.org/home
Citations:
PubMed Identifier
28148635
Citation
Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Steinmiller KC, Griffith LM, Muraro PA, Openshaw H, Sayre PH, Stuve O, Arnold DL, Wener MH, Georges GE, Wundes A, Kraft GH, Bowen JD. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017 Feb 28;88(9):842-852. doi: 10.1212/WNL.0000000000003660. Epub 2017 Feb 1.
Results Reference
background
PubMed Identifier
25546364
Citation
Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Griffith LM, Muraro PA, Openshaw H, Sayre PH, Stuve O, Arnold DL, Spychala ME, McConville KC, Harris KM, Phippard D, Georges GE, Wundes A, Kraft GH, Bowen JD. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report. JAMA Neurol. 2015 Feb;72(2):159-69. doi: 10.1001/jamaneurol.2014.3780.
Results Reference
background
PubMed Identifier
30794930
Citation
Cohen JA, Baldassari LE, Atkins HL, Bowen JD, Bredeson C, Carpenter PA, Corboy JR, Freedman MS, Griffith LM, Lowsky R, Majhail NS, Muraro PA, Nash RA, Pasquini MC, Sarantopoulos S, Savani BN, Storek J, Sullivan KM, Georges GE. Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019 May;25(5):845-854. doi: 10.1016/j.bbmt.2019.02.014. Epub 2019 Feb 19.
Results Reference
background
Links:
URL
https://www.niaid.nih.gov/
Description
National Institute of Allergy and Infectious Diseases (NIAID)
URL
https://www.niaid.nih.gov/about/dait
Description
Division of Allergy, Immunology, and Transplantation (DAIT)
URL
http://www.immunetolerance.org
Description
Immune Tolerance Network (ITN)
URL
http://beat-ms.org/
Description
Visit this ITN Study website for more information

Learn more about this trial

Best Available Therapy Versus Autologous Hematopoetic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS)

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