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Old 01-09-2020, 01:40 PM
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Default Clinical Trial of aHSCT versus Best Available MS treatment begins enrollment

Clinical Trial of Autologous Hematopoietic Stem Cell Transplantation versus Best Available Therapy for Multiple Sclerosis (BEAT-MS) Begins Enrollment

SEATTLE, WA, USA I January 7, 2020 I The Immune Tolerance Network (ITN) opened the BEAT-MS clinical trial for enrollment. BEAT-MS or "Best Available Therapy vs. Autologous Hematopoietic Stem Cell Transplant (AHSCT) for MS" will investigate high dose immunosuppression followed by AHSCT – a type of transplant using a patient's own immune stem cells – compared to the best medical treatment currently available for multiple sclerosis (MS) in participants with relapsing MS.

MS affects nearly 1 million adults in the United States and an estimated 2.3 million individuals worldwide. MS is an autoimmune disease in which the body's immune system attacks the protective myelin that covers nerve fibers in the brain and spinal cord and damages the nerve axons (fibers). As a result, nerve impulses are not transmitted as quickly or efficiently, resulting in symptoms such as difficulty walking, weakness, loss of vision and problems with memory, among other disabilities. Relapsing forms of MS are characterized by periods of time during which symptoms worsen (relapse), followed by periods of time in which symptoms get better (remission). Incomplete recovery from relapses often leads to worsening disability.

More than a dozen therapies have been approved by the FDA for the treatment of relapsing MS. However, despite this availability of an increasing number of treatment options, some patients with highly active disease do not achieve adequate disease control. In addition, side effects of therapy and the risk of relapse if therapy is stopped continue to be significant problems. Previous studies have shown that AHSCT could be an effective and durable treatment for patients with relapsing MS whose disease is incompletely controlled by the currently available therapies.

"Our earlier studies demonstrated the feasibility of AHSCT therapy in severe forms of relapsing MS, leading the way toward this important new trial that will evaluate durability of successful AHSCT treatment compared to alternative therapies," noted Dr. Jerry Nepom, director of the ITN. "Replacing and restarting the immune system is potentially capable of stopping autoimmune diseases such as MS, but requires careful clinical trial evaluation to ensure the appropriate balance of risk and benefit for our patients."

BEAT-MS will be the first clinical trial in which the efficacy, safety, and cost-effectiveness of AHSCT will be directly compared to the best available treatments. The best available treatments are chosen from among those recently approved for the treatment of MS that have not yet been tried by the study participant. Study participants assigned to the group receiving AHSCT will first have their own immune system stem cells mobilized out of the bone marrow, collected from the bloodstream, and then stored in a qualified laboratory for later use. Participants will then receive chemotherapy, which depletes the cells in their immune system that include those cells implicated in causing MS. After the chemotherapy, the participant's own stem cells that were collected earlier will be given back to the participant to create a new population of immune cells.

"There is growing evidence that AHSCT can be a safe and effective treatment option for some people living with MS. The BEAT-MS study is expected to add to our knowledge about AHSCT by comparing the safety and effectiveness of this treatment directly with other powerful MS therapies in a well-designed and properly controlled study," commented Bruce Bebo, PhD, Executive Vice President of Research for the National Multiple Sclerosis Society. "The results could change standards of care for people with some types of MS."

BEAT-MS is being conducted by the ITN, a program of Benaroya Research Institute at Virginia Mason, funded by the National Institute of Allergy and Infectious Diseases (NIAID) under grant award number UM1AI109565, in collaboration with The Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The first open clinical site that will begin recruiting participants for BEAT-MS is Cleveland Clinic. BEAT-MS will be conducted at 19 clinical sites across the United States and in the United Kingdom (U.K.). These sites include the Cleveland Clinic in Cleveland, OH, where Jeffrey Cohen, MD, serves as the protocol chair and lead investigator, in addition to the Fred Hutchinson Cancer Research Center in Seattle, WA, and Imperial College London in London, U.K., where the trial's other two protocol co-chairs, George Georges, MD, and Paolo Muraro, MD, PhD, respectively, will lead the trial. The BMT CTN, funded by the National Heart Lung and Blood Institute and the National Cancer Institute, both components of NIH, is collaborating with the ITN to qualify participating transplant centers.

Additional information about BEAT-MS, NCT04047628, can be found at www.BEAT-MS.org.

About The Immune Tolerance Network
The Immune Tolerance Network (ITN) is a collaborative network for clinical research sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system. Visit www.immunetolerance.org for more information.
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Old 01-17-2020, 02:51 PM
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There are strict inclusion and exclusion criteria. And even if you are selected, there is a 50/50 chance you will be randomized into BAT (best available treatment): natalizumab, alemtuzumab, ocrelizumab, or rituximab. As a Phase 3, this is a critical trial to finally get FDA approval. -D

Criteria....

Ages Eligible for Study: 18 Years to 55 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No

Inclusion Criteria:

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) ≥ 2.0 and ≤ 5.5 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 treatment failure in the 24 months prior to the screening visit (Visit -2). as described below:

Each episode of treatment failure must occur following ≥ 3 months of treatment with an FDA-approved Disease-modifying Therapy (DMT) for relapsing forms of MS, or with rituximab, and
At least one episode of treatment failure must occur with an oral agent or a monoclonal antibody, specifically: dimethyl fumarate (Tecfidera®), teriflunomide (Aubagio®), cladribine (Mavenclad®), daclizumab (Zinbryta®), siponimod (Mayzent®), fingolimod (Gilenya®), rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), or alemtuzumab (Campath®, Lemtrada®), and
At least one episode of treatment failure must have occurred within the 12 months prior to the screening visit (Visit -2), and
At least one episode of treatment failure must be a clinical MS relapse (see item d.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: natalizumab, alemtuzumab, ocrelizumab, and/or rituximab.

--Note: Rituximab and ocrelizumab are considered equivalent for candidacy.Candidacy for treatment for each DMT is defined as meeting all of the following:

No prior treatment failure 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.
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.

---------------

Exclusion Criteria:

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

Diagnosis of primary progressive Multiple Sclerosis (MS) according to the 2017 McDonald criteria
History of neuromyelitis optica or anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies associated encephalomyelitis
Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer
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 natalizumab, alemtuzumab, ocrelizumab, or rituximab between screening visit (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

-Note: 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.
Evidence of HIV infection
Positive QuantiFERON - TB Gold or TB Gold Plus test results (e.g., blood test results that detect infection with Mycobacterium tuberculosis) Note: A Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON - TB Gold or TB Gold Plus 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:

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

Chronic exertional angina, or
Signs or symptoms of congestive heart failure.
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.
Left ventricular ejection fraction (LVEF) < 50%
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
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, 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 by therapy completed at least 5 years prior to randomization (Day 0) will be considered on an individual basis by the study adjudication committee.

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.
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 breast-feeding
Inability or unwillingness to use effective means of birth control
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 mouse, rabbit, or Escherichia coli-derived proteins
Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with gadolinium administration
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:

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.
Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality, or
Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
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