A Multicenter Randomized Controlled Trial of Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Treatment-Resistant Relapsing Multiple Sclerosis (ITN077AI)

Who is this study for? Patients with Multiple Sclerosis
Status: Recruiting
Location: See all (22) locations...
Intervention Type: Biological, Procedure
Study Type: Interventional
Study Phase: Phase 3
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).

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 55
Healthy Volunteers: No
View:

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

⁃ Diagnosis of Multiple Sclerosis (MS) according to the 2017 McDonald Criteria

⁃ (Kurtzke) Expanded Disability Status Scale (EDSS) ≤ 6.0 at the time of randomization (Day 0)

⁃ 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.

⁃ 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:

⁃ 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

⁃ 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 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).

⁃ 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.

⁃ Completion of SARS-CoV-2 vaccination series ≥ 14 days prior to randomization (Day 0).

⁃ 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).

⁃ Insurance or public funding approval for MS treatment with at least one candidate DMT, and

⁃ Ability to comply with study procedures and provide informed consent, in the opinion of the investigator.

Locations
United States
California
Stanford Multiple Sclerosis Center
Recruiting
Palo Alto
Colorado
Rocky Mountain Multiple Sclerosis Center, University of Colorado School of Medicine
Recruiting
Aurora
Massachusetts
University of Massachusetts Memorial Medical Center
Recruiting
Worcester
Minnesota
University of Minnesota Multiple Sclerosis Center
Recruiting
Minneapolis
Mayo Clinic
Recruiting
Rochester
Missouri
John L. Trotter Multiple Sclerosis Center, Washington University School of Medicine in St. Louis
Not yet recruiting
Saint Louis
Washington University
Recruiting
Saint Louis
North Carolina
Duke University Medical Center
Recruiting
Durham
New York
Baird Multiple Sclerosis (MS) Center, Kaleida Health
Not yet recruiting
Buffalo
Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Siinai
Recruiting
New York
Rochester Multiple Sclerosis Center, University of Rochester
Not yet recruiting
Rochester
Ohio
University of Cincinnati (UC) Waddell Center for Multiple Sclerosis
Recruiting
Cincinnati
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic
Recruiting
Cleveland
Oregon
Multiple Sclerosis Center, Oregon Health & Science University
Recruiting
Portland
Pennsylvania
Penn Comprehensive MS Center, Hospital of the University of Pennsylvania
Recruiting
Philadelphia
Texas
University of Texas Southwestern Medical Center: Division of Multiple Sclerosis and Neuroimmunology
Not yet recruiting
Dallas
Maxine Mesigner Multiple Sclerosis Comprehensive Care Center, Baylor College of Medicine Medical Center
Not yet recruiting
Houston
Virginia
Virginia Commonwealth University Multiple Sclerosis Treatment and Research Center
Recruiting
Richmond
Washington
Clinical Research Division, Fred Hutchinson Cancer Research Center
Recruiting
Seattle
Multiple Sclerosis Center at Northwest Hospital
Recruiting
Seattle
Multiple Sclerosis Center, Swedish Neuroscience Institute
Recruiting
Seattle
Other Locations
United Kingdom
Imperial College Healthcare NHS Trust
Not yet recruiting
London
Time Frame
Start Date: December 19, 2019
Estimated Completion Date: October 2029
Participants
Target number of participants: 156
Treatments
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.
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).
Authors
Sponsors
Collaborators: PPD, Blood and Marrow Transplant Clinical Trials Network, Rho Federal Systems Division, Inc., Immune Tolerance Network (ITN)
Leads: National Institute of Allergy and Infectious Diseases (NIAID)

This content was sourced from clinicaltrials.gov

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