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Stem Cell Transplant

Stem Cell Transplant vs Best Available Therapy for Multiple Sclerosis (BEAT-MS Trial)

Phase 3
Recruiting
Research Sponsored by National Institute of Allergy and Infectious Diseases (NIAID)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
T2 abnormalities on brain Magnetic Resonance Imaging (MRI) that fulfill the 2017 McDonald MRI criteria for dissemination in space
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)
Must not have
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)
Timeline
Screening 3 weeks
Treatment Varies
Follow Up from visit pre-r up to 72 months (6 years)
Awards & highlights
No Placebo-Only Group
Pivotal Trial

Summary

This trial is testing whether AHSCT is better than BAT for treating people with MS who have not responded to other treatments. 156 people will be randomly assigned to either AHSCT or BAT, and followed for 72 months.

Who is the study for?
This trial is for adults aged 18-55 with treatment-resistant relapsing Multiple Sclerosis (MS), as per the McDonald Criteria, who've had at least two episodes of disease activity in the past three years despite treatment. Participants must have an EDSS score ≤6.0, be vaccinated against COVID-19 and varicella zoster, and agree to contraception use.
What is being tested?
The BEAT-MS trial compares Autologous Hematopoietic Stem Cell Transplantation (AHSCT) with Best Available Therapy (BAT) for MS that hasn't responded well to other treatments. It's a blinded study where participants are randomly assigned to one of these strategies in equal numbers.
What are the potential side effects?
Potential side effects from AHSCT may include infection risks due to immune system suppression, reactions related to stem cell infusion, and infertility. BAT side effects vary depending on the specific therapy used but can include flu-like symptoms, injection site reactions, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My brain MRI shows changes that meet specific criteria for a diagnosis.
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I completed my COVID-19 vaccination series more than 14 days ago.
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I have been diagnosed with Multiple Sclerosis according to the latest criteria.
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My disability level allows me to walk at least 100 meters without aid or rest.
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My MS worsened despite taking approved medication for over a month.
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I am between 18 and 55 years old.
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My brain MRI shows specific changes that meet certain criteria for a diagnosis.
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I can walk with a cane for 100 meters without help.
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My condition has worsened or shown activity in the last year.
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I am a candidate for high efficacy MS treatments like cladribine or natalizumab.
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My MS has worsened twice or more in the last 3 years despite treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I have been diagnosed with PML based on brain MRI or CSF tests.
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I have a history of low blood cell counts due to MDS.
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I have had a solid organ transplant in the past.
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I have a history of sickle cell anemia or similar blood disorders.
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I have had an acute MS flare-up or steroid treatment within the last month.
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I have had a stem cell transplant before.
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I currently have an active stomach ulcer.
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I have or had a serious autoimmune disease that needed treatment.
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My diabetes is not well-managed, with an HbA1c level over 8%.
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I do not have any active infections, including viral, bacterial, or fungal.
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My kidney function is reduced with an eGFR below 60.
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I have been diagnosed with primary progressive MS.
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I have a history of neuromyelitis optica or MOG antibody disease.
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I have or had liver cirrhosis.
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I have or had a neurological disorder.
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My liver condition meets specific health criteria.
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I have had a stroke or similar brain blood flow problem.
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I have or had a serious heart condition.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~from visit pre-r up to 72 months (6 years)
This trial's timeline: 3 weeks for screening, Varies for treatment, and from visit pre-r up to 72 months (6 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Multiple Sclerosis (MS) Relapse-Free Survival
Secondary study objectives
Change in Serum Neurofilament Light Chain (NfL) Concentration
Number of Multiple Sclerosis (MS) Relapses Per Year
Proportion of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) Recipients Who Experience Primary or Secondary Graft Failure
+9 more

Side effects data

From 2022 Phase 3 trial • 665 Patients • NCT00567567
84%
58300-Neutrophil count decreased
70%
65800-Platelet count decreased
20%
43100-Hypokalemia
18%
44800-Infections and infestations - Other specify
18%
33300-Febrile neutropenia
17%
88500-White blood cell decreased
13%
13200-Anemia
9%
55600-Mucositis oral
7%
42700-Hypocalcemia
7%
13500-Anorexia
7%
11600-Alanine aminotransferase increased
7%
41400-Hyperglycemia
6%
15000-Aspartate aminotransferase increased
6%
43300-Hyponatremia
6%
73700-Sepsis
6%
53700-Lymphocyte count decreased
4%
25700-Diarrhea
3%
65900-Pleural effusion
3%
57600-Nausea
3%
37500-GGT increased
3%
41600-Hyperkalemia
3%
10300-Abdominal pain
3%
20500-Catheter related infection
3%
59700-Oral pain
2%
38900-Hearing impaired
2%
43900-Hypoxia
2%
17200-Blood and lymphatic system disorders - Other specify
2%
14900-Ascites
2%
75700-Small intestinal obstruction
2%
87900-Vomiting
2%
43600-Hypotension
1%
45800-INR increased
1%
34000-Fibrinogen decreased
1%
23000-Confusion
1%
42600-Hypoalbuminemia
1%
69700-Rash maculo-papular
1%
71500-Respiratory failure
1%
73900-Serum amylase increased
1%
26600-Duodenal obstruction
1%
66300-Pneumonitis
1%
58000-Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify
1%
56600-Myelitis
1%
75600-Small intestinal mucositis
1%
66800-Postoperative hemorrhage
1%
43500-Hypophosphatemia
1%
37300-Generalized muscle weakness
1%
81200-Treatment related secondary malignancy
1%
31200-Esophagitis
1%
83100-Urinary tract infection
1%
24100-Creatinine increased
1%
11100-Acute kidney injury
1%
62600-Pelvic pain
1%
65300-Pharyngolaryngeal pain
1%
31900-Eye disorders - Other specify
1%
10900-Activated partial thromboplastin time prolonged
1%
11800-Alkaline phosphatase increased
1%
42500-Hyperuricemia
1%
17400-Blood bilirubin increased
1%
63100-Pericardial effusion
1%
72700-Right ventricular dysfunction
1%
37200-General disorders and administration site conditions - Other specify
1%
40000-Hepatic failure
1%
88200-Weight gain
1%
41300-Hypercalcemia
1%
54900-Metabolism and nutrition disorders - Other specify
1%
71000-Renal and urinary disorders - Other specify
1%
69000-Pulmonary hypertension
1%
20100-Cardiac disorders - Other specify
1%
22100-Colitis
1%
44200-Ileal obstruction
1%
81900-Typhlitis
1%
33900-Fever
1%
35500-Gallbladder pain
1%
40600-Hepatobiliary disorders - Other specify
1%
66500-Portal hypertension
1%
12000-Allergic reaction
1%
13100-Anaphylaxis
1%
44700-Immune system disorders - Other specify
1%
13400-Anorectal infection
1%
25600-Device related infection
1%
29500-Enterocolitis infectious
1%
53100-Lung infection
1%
62500-Pelvic infection
1%
75200-Skin infection
1%
82300-Upper respiratory infection
1%
14500-Arterial injury
1%
15300-Ataxia
1%
38800-Headache
1%
63900-Peripheral motor neuropathy
1%
11300-Adult respiratory distress syndrome
1%
29700-Epistaxis
1%
78100-Stridor
1%
68400-Pruritus
1%
51700-Left ventricular systolic dysfunction
1%
27800-Dyspnea
1%
58100-Nervous system disorders - Other specify
1%
29000-Encephalopathy
1%
42100-Hypertension
1%
24700-Dehydration
1%
43200-Hypomagnesemia
1%
31800-Extrapyramidal disorder
1%
52600-Lipase increased
1%
10700-Acidosis
100%
80%
60%
40%
20%
0%
Study treatment Arm
Tandem HST (CEM), Randomly Assigned
Single HST (CEM)
Not Assigned

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups
Experimental Treatment
Active Control
Group I: AHSCTExperimental Treatment1 Intervention
AHSCT: Myeloablative and Immunoablative therapy followed by Autologous Hematopoietic Stem Cell Transplantation Participants will undergo: 1. 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. 2. 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. 3. 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.
Group II: Best Available Therapy (BAT)Active Control1 Intervention
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).
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Autologous Hematopoietic Stem Cell Transplantation
2017
Completed Phase 3
~2090

Find a Location

Who is running the clinical trial?

PPD DEVELOPMENT, LPIndustry Sponsor
163 Previous Clinical Trials
37,159 Total Patients Enrolled
3 Trials studying Multiple Sclerosis
235 Patients Enrolled for Multiple Sclerosis
National Institute of Allergy and Infectious Diseases (NIAID)Lead Sponsor
3,336 Previous Clinical Trials
5,382,678 Total Patients Enrolled
16 Trials studying Multiple Sclerosis
4,086 Patients Enrolled for Multiple Sclerosis
Immune Tolerance Network (ITN)NETWORK
67 Previous Clinical Trials
7,702 Total Patients Enrolled
5 Trials studying Multiple Sclerosis
342 Patients Enrolled for Multiple Sclerosis
Blood and Marrow Transplant Clinical Trials NetworkNETWORK
50 Previous Clinical Trials
14,398 Total Patients Enrolled
PPDIndustry Sponsor
161 Previous Clinical Trials
36,235 Total Patients Enrolled
3 Trials studying Multiple Sclerosis
235 Patients Enrolled for Multiple Sclerosis
Rho Federal Systems Division, Inc.Industry Sponsor
43 Previous Clinical Trials
14,807 Total Patients Enrolled
2 Trials studying Multiple Sclerosis
380 Patients Enrolled for Multiple Sclerosis
Jeffrey A. Cohen, MDStudy ChairMellen Center for MS Treatment and Research, Cleveland Clinic
2 Previous Clinical Trials
354 Total Patients Enrolled
1 Trials studying Multiple Sclerosis
350 Patients Enrolled for Multiple Sclerosis
George E. Georges, MDStudy ChairNorthwestern University
1 Previous Clinical Trials
25 Total Patients Enrolled
1 Trials studying Multiple Sclerosis
25 Patients Enrolled for Multiple Sclerosis
Paolo A. Muraro, MD, PhDStudy ChairDepartment of Medicine, Imperial College London

Media Library

Autologous Hematopoietic Stem Cell Transplantation (Stem Cell Transplant) Clinical Trial Eligibility Overview. Trial Name: NCT04047628 — Phase 3
Multiple Sclerosis Research Study Groups: AHSCT, Best Available Therapy (BAT)
Multiple Sclerosis Clinical Trial 2023: Autologous Hematopoietic Stem Cell Transplantation Highlights & Side Effects. Trial Name: NCT04047628 — Phase 3
Autologous Hematopoietic Stem Cell Transplantation (Stem Cell Transplant) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04047628 — Phase 3
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