Stem Cell Transplant vs Best Available Therapy for Multiple Sclerosis

(BEAT-MS Trial)

Recruiting at 23 trial locations

Overseen By James D. Bowen, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Oral DMTs, Monoclonal antibodies

Must not be taking: Investigational agents, Antiarrhythmia therapy

Disqualifiers: Primary progressive MS, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

156 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for people with multiple sclerosis (MS) who haven't responded well to other therapies. The study compares a stem cell transplant method, known as Autologous Hematopoietic Stem Cell Transplantation, which uses a person's own cells, to the best available medications for MS. It seeks participants who have experienced multiple flare-ups of MS symptoms despite trying other treatments. Researchers will follow participants for six years to determine which treatment works best. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking MS treatments.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants should not have started any new high efficacy treatments between certain visits, and there are specific requirements for those using medicinal or recreational marijuana.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is generally safe for people with multiple sclerosis (MS). In one study, 68% of patients experienced no disease activity after treatment, which is encouraging. Another study from Denmark found this treatment effective with few serious side effects and no reported deaths among patients.

Safety information for the Best Available Therapy (BAT) group can vary depending on the specific drug used. Most of these drugs, such as Cladribine, Natalizumab, and Ocrelizumab, have already received FDA approval for treating MS, indicating they have been tested for safety in many people. While each drug carries its own risks, patients usually tolerate them well.

In summary, both AHSCT and the drugs used in BAT have demonstrated good safety records in studies, offering reassurance to those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for multiple sclerosis (MS) because it offers a fresh approach compared to conventional therapies. Unlike standard treatments that primarily target inflammation or immune system components, AHSCT aims to reset the immune system entirely by using the patient's own stem cells. This process involves collecting and reinfusing stem cells after intensive chemotherapy to eliminate the problematic immune cells. This method has the potential to not just halt disease progression but possibly regenerate damaged tissues, offering hope for longer-lasting remission or even reversal of symptoms.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that using a patient's own stem cells, a process called Autologous Hematopoietic Stem Cell Transplantation (AHSCT), can effectively treat multiple sclerosis (MS). Studies have found that AHSCT greatly helps patients with severe relapsing MS by reducing disease activity and improving their ability to function. Long-term results from earlier patients indicate lasting benefits and manageable side effects. Specifically, patients who received AHSCT experienced fewer relapses and slower disease progression compared to those on other treatments.

In this trial, participants will be randomized to receive either AHSCT or Best Available Therapy (BAT). For the BAT arm, medications like cladribine, natalizumab, and ocrelizumab have proven effective in reducing relapses and slowing the progression of MS. These treatments are well-regarded in the MS community for managing symptoms and improving quality of life. Both AHSCT and BAT offer promising options for those with MS resistant to other treatments. ^{2 3 5 6 7}

Who Is on the Research Team?

Jeffrey A. Cohen, MD

Principal Investigator

Mellen Center for MS Treatment and Research, Cleveland Clinic

George E. Georges, MD

Principal Investigator

Northwestern University

Paolo A. Muraro, MD, PhD

Principal Investigator

Department of Medicine, Imperial College London

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My brain MRI shows changes that meet specific criteria for a diagnosis.

I am willing to switch to MARINOL® if needed for the study.

My insurance covers MS treatment with a specific drug.

Exclusion Criteria

I have been diagnosed with PML based on brain MRI or CSF tests.

Positive pregnancy test or breastfeeding

I have a history of low blood cell counts due to MDS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization and Graft Collection

Mobilization of peripheral blood stem cells with cyclophosphamide, filgrastim, and dexamethasone. The autologous graft will be collected by leukapheresis and cryopreserved.

Approximately 4 weeks

Conditioning and Transplantation

High dose myeloablative and immunoablative conditioning with a six-day BEAM chemotherapy and rabbit anti-thymocyte globulin regimen, followed by autologous cryopreserved graft infusion.

6 days for conditioning, followed by immediate transplantation

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of MS relapse-free survival and other secondary outcomes.

72 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Hematopoietic Stem Cell Transplantation
• Best Available Therapy (BAT)

Trial Overview 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.

How Is the Trial Designed?

Group I: AHSCT Experimental Treatment 1 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 Control 1 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).

Autologous Hematopoietic Stem Cell Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Autologous Hematopoietic Stem Cell Transplantation for:

• Various hematologic malignancies including non-Hodgkin lymphoma, multiple myeloma, and leukemia

Approved in European Union as Autologous Stem Cell Transplant for:

• Non-Hodgkin lymphoma
• Multiple myeloma
• Leukemia
• Other hematologic malignancies

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Industry Sponsor

Immune Tolerance Network (ITN)

Collaborator

Trials

68

Recruited

7,900+

Blood and Marrow Transplant Clinical Trials Network

Collaborator

Trials

51

Recruited

14,600+

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials

44

Recruited

15,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40500866/

Autologous haematopoietic stem cell transplantation for ... Autologous haematopoietic stem cell transplantation (AHSCT) has been developed as a treatment for multiple sclerosis (MS) since 1995.

2. nature.com nature.com/articles/s41582-024-01050-x

Autologous haematopoietic stem cell transplantation for ... Long-term outcomes in a large cohort of patients treated with AHSCT for MS were first reported in a retrospective joint analysis of the EBMT and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2211034823003310

Autologous hematopoietic stem cell transplantation of ... AHSCT of patients with aggressive RRMS was an effective and relatively safe treatment with few serious AEs and no mortality in Danish patients.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ana.27247

Effectiveness of Autologous Hematopoietic Stem Cell ... Objective. To compare clinical and radiological outcomes among relapsing multiple sclerosis patients treated with autologous hematopoietic stem ...

5. astctjournal.org astctjournal.org/article/S1083-8791(19)30139-9/fulltext

Biology of Blood and Marrow Transplantation Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9333355/

Autologous Hematopoietic Stem-Cell Transplantation in ... Our meta-analysis showed that 68% of patients with MS experience no evidence of disease activity (NEDA) after AHSCT (95% CI 59%, 77).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12301330/

Safety and long-term efficacy of autologous hematopoietic cell ... We aimed to assess the safety and long-term efficacy of HCT modality for severe SSc, refractory to conventional therapy, in 17 patients who were ...