Stem Cell Transplant vs Best Available Therapy for Multiple Sclerosis

(BEAT-MS Trial)

Recruiting at 22 trial locations

Overseen By Bruce Cohen, 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

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the treatment Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis?

Research shows that Autologous Hematopoietic Stem Cell Transplantation (AHSCT) can be effective for aggressive forms of multiple sclerosis that do not respond to standard treatments, providing long periods without disease progression. Studies have demonstrated its feasibility and potential benefits, especially in severe cases with active disease signs. ^{1 2 3 4 5}

Is autologous stem cell transplant safe for humans?

Autologous stem cell transplant has been studied for multiple sclerosis and is generally considered safe, though it carries a risk of mortality that has decreased to 2-3% in recent years. Supportive care is important to ensure the treatment is well-tolerated. ^{2 3 6 7 8}

How is the treatment Autologous Hematopoietic Stem Cell Transplantation different from other treatments for multiple sclerosis?

Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is unique because it involves using a patient's own stem cells to reset the immune system, which can provide long-lasting relief for those with aggressive multiple sclerosis that doesn't respond to standard therapies. Unlike typical medications, this treatment aims to halt disease progression by rebuilding the immune system from scratch. ^{1 2 4 8 9}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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+

Findings from Research

In a phase II trial involving 15 patients with advanced multiple sclerosis, CD34+ selected autologous stem cell transplantation (ASCT) showed acceptable toxicity and resulted in stabilization or improvement of disability status in some patients after one year.

Despite some complications like engraftment syndrome and transient neurologic deterioration, the treatment demonstrated a reduction in disease progression, with MRI showing disappearance of certain lesions, indicating potential efficacy in managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients. Carreras, E., Saiz, A., Marín, P., et al.[2006]

Autologous Stem Cell Transplant (ASCT) is a safe procedure for multiple sclerosis patients, even those with higher disability scores, as demonstrated in a study of 20 patients with no reported mortality and effective management of febrile neutropenia.

The study found that 6 out of 19 patients showed improvement in their disability scores, particularly those with relapsing-remitting multiple sclerosis (RRMS), indicating that ASCT may be more beneficial for patients with active disease compared to those with secondary progressive multiple sclerosis (SPMS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplant in adult multiple sclerosis patients: A study from North India. Dayama, A., Bhargava, R., Kurmi, SR., et al.[2022]

Autologous haematopoietic stem-cell transplantation has been explored as a treatment for severe multiple sclerosis in over 400 patients, showing promising efficacy particularly in rapidly evolving cases with active MRI signs.

While the risk of transplant-related mortality has decreased to 2-3%, it remains a significant concern, highlighting the need for careful patient selection based on disease phase and conditioning regimen intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem-cell transplantation in multiple sclerosis: benefits and risks. Capello, E., Vuolo, L., Gualandi, F., et al.[2009]

In a study of 10 patients with highly inflammatory multiple sclerosis (MS) treated with autologous hematopoietic stem cell transplantation (aHSCT) over a median follow-up of 2.4 years, five out of six patients with mild to moderate disability showed improvement, while those with chronic progressive MS did not benefit from the treatment.

The systematic review indicated that aHSCT is more effective in younger, less disabled MS patients with active inflammation, supporting its safety and efficacy as a treatment option for selected patients, although further randomized controlled trials are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stem cell transplantation for multiple sclerosis. Hamburg experiences and state of international research]. Stellmann, JP., Stürner, KH., Ufer, F., et al.[2018]

In a study of 281 patients with aggressive forms of multiple sclerosis (MS) who underwent autologous hematopoietic stem cell transplantation (AHSCT), 46% remained free from neurological progression five years post-transplant, indicating AHSCT's potential long-term efficacy.

The study found that younger age, having a relapsing form of MS, fewer previous treatments, and a lower baseline disability score (EDSS) were associated with better outcomes, suggesting that patient selection may influence the success of AHSCT in treating MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. Muraro, PA., Pasquini, M., Atkins, HL., et al.[2022]

Autologous haematopoietic stem cell therapy (AHSCT) has emerged as a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS), particularly in patients who do not respond to conventional therapies.

The safety and efficacy of AHSCT have improved significantly due to better patient selection, increased experience at transplant centers, and the importance of supportive care throughout the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation. Ismail, A., Sharrack, B., Saccardi, R., et al.[2020]

In a study of 48 patients with aggressive multiple sclerosis treated with autologous haematopoietic stem cell transplantation (HSCT), the treatment showed high efficacy with an 87% relapse-free survival rate at 5 years and a 68% disease-free survival rate.

HSCT was performed safely, with no reported mortality; however, common long-term side effects included herpes zoster reactivation in 15% of patients and thyroid disease in 8.4%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. Burman, J., Iacobaeus, E., Svenningsson, A., et al.[2022]

Autologous hematopoietic stem cell transplant (AHSCT) has shown high efficacy and durable outcomes in patients with relapsing multiple sclerosis, particularly for those with aggressive disease that does not respond to standard therapies.

Recent improvements in the safety of AHSCT have led to lower mortality rates, making it a viable option for younger patients (under 50 years) with shorter disease duration (less than 10 years), although further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society. Miller, AE., Chitnis, T., Cohen, BA., et al.[2022]

In a study involving 10 patients with rapidly evolving secondary progressive multiple sclerosis (MS), autologous hematopoietic stem cell transplantation (ASCT) following a conditioning regimen effectively eliminated gadolinium-enhancing lesions on MRI, indicating a strong suppression of disease activity.

While patients showed a decrease in MRI lesions and some clinical improvement or stability, the long-term effects of ASCT on the overall disease course of MS are still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. Mancardi, GL., Saccardi, R., Filippi, M., et al.[2019]

References

1. Italy pubmed.ncbi.nlm.nih.gov

CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients. [2006]

2. India pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplant in adult multiple sclerosis patients: A study from North India. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem-cell transplantation in multiple sclerosis: benefits and risks. [2009]

4. Germany pubmed.ncbi.nlm.nih.gov

[Stem cell transplantation for multiple sclerosis. Hamburg experiences and state of international research]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS. [2019]