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

• ClinicalTrials.gov Identifier: NCT04047628
• Recruitment Status: Recruiting
• First Posted: August 7, 2019
• Last Update Posted: March 3, 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.
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

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).

Condition or disease	Intervention/treatment	Phase
Relapsing Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Biological: Best Available Therapy (BAT)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter Randomized Controlled Trial of Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (ITN077AI)
• Actual Study Start Date: December 19, 2019
• Estimated Primary Completion Date: October 2026
• Estimated Study Completion Date: October 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: AHSCT; 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.	Procedure: Autologous Hematopoietic Stem Cell Transplantation; 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.; Other Name: AHSCT
Active Comparator: Best Available Therapy (BAT); Participants randomized to BAT: Best available therapy will be selected by the Site Investigator from: Cladribine (Mavenclad®), natalizumab (Tysabri®), alemtuzumab (Campath®, Lemtrada®), ocrelizumab (Ocrevus®), rituximab (Rituxan®), or ofatumumab (Arzerra®) (after approval by the FDA for relapsing MS).	Biological: Best Available Therapy (BAT); Disease-modifying therapy (DMT) selected by the Site Investigator from the below: cladribine; natalizumab; alemtuzumab; ocrelizumab,; rituximab, or; ofatumumab; Other Names: natalizumab (Tysabri®); alemtuzumab (Campath®, Lemtrada®); ocrelizumab (Ocrevus®); rituximab (Rituxan®); cladribine (Mavenclad®); ofatumumab (Kesimpta®)

Outcome Measures

Primary Outcome Measures :

1. Multiple Sclerosis (MS) Relapse-Free Survival [ Time Frame: From Day 0 (Randomization to Treatment) Up to 36 Months (3 Years) ]
   MS relapse-free survival, analyzed as time from treatment randomization until MS relapse or death from any cause.

Secondary Outcome Measures :

1. Number of Multiple Sclerosis (MS) Relapses Per Year [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]
   Annual Relapse Rate (ARR) time calculated as number of confirmed relapses divided by time in study per year.
2. The Occurrence of Any Evidence of Multiple Sclerosis (MS) Disease Activity or Death From Any Cause [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]
   The occurrence of any evidence of MS disease activity or death from any cause, analyzed as time-to-event.
3. The Occurence of Confirmed Disability Worsening by the Kurtz Expanded Disability Status Scale (EDSS) [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]

   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).
4. The Occurrence of Confirmed Disability Improvement by the Kurtz Expanded Disability Status Scale (EDSS) [ Time Frame: Day 0 (Randomization to Treatment) Up to Month 72 (6 Years) ]

   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).
5. Whole Brain Volume Change from Pre-Randomization Visit to the follow-up evaluations [ Time Frame: From Visit Pre-R Up to 72 Months (6 Years) ]
   Method of assessment: Magnetic Resonance Imaging (MRI) imaging.
6. Change in Serum Neurofilament Light Chain (NfL) Concentration [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]
   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.
7. The Occurrence of Death From Any Cause: All-Cause Mortality [ Time Frame: Day 0 (Randomization to Treatment) Up to Month 72 (6 Years) ]
   Any death, regardless of relationship to treatment.
8. Proportion of Participants who Experience a Serious Adverse Event (SAE) [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]

   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)

9. Proportion of Participants with a Grade 3 or Higher Infection [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]
   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.
10. Proportion of Participants with Progressive Multifocal Leukoencephalopathy (PML) [ Time Frame: From Day 0 (Randomization to Treatment) Up to 72 Months (6 Years) ]

    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).

11. Time to Neutrophil Engraftment Among Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients [ Time Frame: From Day of Graft Infusion (Receipt of Peripheral Blood Stem Cells-PBSC Infusion) Up to 72 Months (6 Years) ]
    Neutrophil engraftment is defined as absolute neutrophil count (ANC) > 500/µl on two consecutive measurements on different days.
12. Proportion of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients Who Experience Primary or Secondary Graft Failure [ Time Frame: From Day of Transplant (Receipt of Peripheral Blood Stem Cells-PBSC Infusion) Up to Day 28 Post Transplant ]

    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Stanford Multiple Sclerosis Center; Recruiting

Palo Alto, California, United States, 94304

Contact: Sujatha Kalle 650-319-5522 skalle@stanford.edu

Principal Investigator: Jeffrey Dunn, MD, FAAN

United States, Colorado

Rocky Mountain Multiple Sclerosis Center, University of Colorado School of Medicine; Recruiting

Aurora, Colorado, United States, 80045

Contact: Sarah Bausano 303-724-3021 neuroresearch@cuanschutz.edu

Principal Investigator: John R. Corboy, MD

United States, Massachusetts

University of Massachusetts Memorial Medical Center; Recruiting

Worcester, Massachusetts, United States, 01655

Contact: Nimmy Kanichai Francis, PhD,MBBS 774-441-7695 Nimmy.KanichaiFrancis@umassmed.edu

Principal Investigator: Carolina Ionete, MD, PhD

United States, Minnesota

University of Minnesota Multiple Sclerosis Center; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Emily Harper 651-333-0841 harpe442@umn.edu

Principal Investigator: Adam Carpenter, MD

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Christina McCarthy 507-284-4423 mccarthy.christina@mayo.edu

Principal Investigator: B. Mark Keegan, MD,FRCPC

United States, Missouri

John L. Trotter Multiple Sclerosis Center, Washington University School of Medicine in St. Louis; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Laura Teeter 314-747-6247 lteeter@wustl.edu

Principal Investigator: Gregory Wu, MD, PhD

United States, New York

Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Siinai; Recruiting

New York, New York, United States, 10029

Contact: Susan Filomena 212-241-3841 susan.e.filomena@mssm.edu

Principal Investigator: Aaron Miller, MD

Rochester Multiple Sclerosis Center, University of Rochester; Not yet recruiting

Rochester, New York, United States, 14620

Principal Investigator: Andrew D. Goodman, MD

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Debbie Dahnke, NRC, RN 919-684-1590 deborah.dahnke@duke.edu

Contact: Katherine Beck, CRC, RN, BSN 919-668-2278 kate.beck@duke.edu

Principal Investigator: Suma Shah, MD

United States, Ohio

University of Cincinnati (UC) Waddell Center for Multiple Sclerosis; Recruiting

Cincinnati, Ohio, United States, 45219

Contact: Tiffany Rupert, CCRC 513-558-0269 BEATMSResearch@UCHealth.com

Principal Investigator: Aram Zabeti, MD

Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Michelle Glazer 216-445-9855 glazerm@ccf.org

Principal Investigator: Jeffrey A. Cohen, MD

United States, Oregon

Multiple Sclerosis Center, Oregon Health & Science University; Recruiting

Portland, Oregon, United States, 97239

Contact: Debbie Guess, RN 503-494-7651 griffide@ohsu.edu

Principal Investigator: Yadav Vijayshree, MD,MCR,FANA,FAAN

United States, Pennsylvania

Penn Comprehensive MS Center, Hospital of the University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: MS MS Clinical Research Team 215-906-4778 msresearch@pennmedicine.upenn.edu

Principal Investigator: Amit Bar-Or, MD,FRCP,FAAN,FANA

United States, Texas

University of Texas Southwestern Medical Center: Division of Multiple Sclerosis and Neuroimmunology; Recruiting

Dallas, Texas, United States, 75390

Contact: Manual Huichapa 214-645-8216 manuel.huichapa@utsoutwestern.edu

Principal Investigator: Benjamin Greenberg, MD

Maxine Mesigner Multiple Sclerosis Comprehensive Care Center, Baylor College of Medicine Medical Center; Not yet recruiting

Houston, Texas, United States, 77030

Contact: Tahari Griffin 713-798-6097 tgriffin@bcm.edu

Principal Investigator: George J. Hutton, MD

United States, Virginia

Virginia Commonwealth University Multiple Sclerosis Treatment and Research Center; Recruiting

Richmond, Virginia, United States, 23219

Contact: Unsong Oh, MD 804-828-3067 unsong.oh@vcuhealth.org

Principal Investigator: Unsong Oh, MD

United States, Washington

Clinical Research Division, Fred Hutchinson Cancer Research Center; Recruiting

Seattle, Washington, United States, 98109

Contact: Bernadette McLaughlin 206-667-4916 bmclaugh@fredhutch.org

Principal Investigator: George E. Georges, MD

Multiple Sclerosis Center, Swedish Neuroscience Institute; Recruiting

Seattle, Washington, United States, 98122

Contact: Bernadette McLaughlin 206-667-4916 bmclaugh@fredhutch.org

Principal Investigator: James D. Bowen, MD

Multiple Sclerosis Center at Northwest Hospital; Recruiting

Seattle, Washington, United States, 98133

Contact: Bernadette McLaughlin 206-667-4916 bmclaugh@fredhutch.org

Principal Investigator: Annette Wundes, MD

United Kingdom

Imperial College Healthcare NHS Trust; Not yet recruiting

London, United Kingdom, W12 0NN

Principal Investigator: Paolo A. Muraro, MD,PhD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Blood and Marrow Transplant Clinical Trials Network

PPD

Rho Federal Systems Division, Inc.

Investigators

• Study Chair: Jeffrey A. Cohen, MD; Mellen Center for MS Treatment and Research, Cleveland Clinic
• Study Chair: George E. Georges, MD; Fred Hutchinson Cancer Center
• Study Chair: Paolo A. Muraro, MD, PhD; Department of Medicine, Imperial College London

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) 

Division of Allergy, Immunology, and Transplantation (DAIT) 

Immune Tolerance Network (ITN) 

Visit this ITN Study website for more information 

Publications:

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.

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.

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT04047628
• Other Study ID Numbers: DAIT ITN077AI; UM1AI109565 ( U.S. NIH Grant/Contract ); NIAID CRMS ID#: 38573 ( Other Identifier: DAIT NIAID ); BMT CTN 1905 ( Other Identifier: Bone Marrow and Transplant Clinical Trials Network (BMT CTN) )
• First Posted: August 7, 2019
• Last Update Posted: March 3, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Participant level data access and additional relevant materials will be made available upon completion of the trial.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code
• Time Frame: After completion of the trial, within 24 months status post database lock.

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.

• URL: https://www.immport.org/home

• 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

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

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

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Alemtuzumab; Ofatumumab; Cladribine; Ocrelizumab; Natalizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunosuppressive Agents