Multiple Sclerosis Treatment With Autologous Hematopoietic Stem Cell Transplantation in the Netherlands (MS-ACT)

Multiple Sclerosis Treatment With Autologous Hematopoietic Stem Cell Transplantation (MS-ACT): A Long-term Prospective Observational Study in the Netherlands

The goal of this observational study is to study the long-term effects of autologous hematopoietic stem cell transplantation (aHSCT) in people with highly active relapsing-remitting multiple sclerosis. The study will evaluate the following items:

1. Disease activity
2. Safety and tolerability of aHSCT
3. Changes in the immune system

Participants will be subjected to frequent visits for five years after treatment with aHSCT. During these visits, clinical testing, evaluation by questionnaires, MRI scans and blood sampling will be performed.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis, Relapsing-Remitting

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Rick Heijnen, MSc; Phone Number: +31627228507; Email: r.m.heijnen@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC
    • Contact: Rick Heijnen, MSc; Phone Number: +31627228507; Email: r.m.heijnen@amsterdamumc.nl
    • Sub-Investigator: R.M. Heijnen, MSc
    • Sub-Investigator: Z.L.E. Van Kempen, MSc, PhD
    • Principal Investigator: J. Killestein, MSc, PhD
  • Nieuwegein, Netherlands
    • Recruiting
    • St. Antonius Hospital
    • Contact: Rick Heijnen, MSc; Phone Number: +31627228507; Email: r.m.heijnen@amsterdamumc.nl
    • Principal Investigator: E.L.J. Hoogervorst, MSc, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with highly active relapsing-remitting multiple sclerosis are eligible for treatment with aHSCT in the Netherlands if they meet the criteria as defined by the Dutch National Health Care Institute.

Description

Inclusion Criteria:

• All patients approved for treatment with aHSCT in the Netherlands in accordance with the Dutch criteria for aHSCT treatment for RRMS

Exclusion Criteria:

• Contra-indications for treatment with aHSCT such as known hypersensitivity to the medication used for aHSCT
• Clinically relevant comorbidities preventing safe use of medication used for aHSCT
• Severe clinical depression
• Active addiction to drugs or alcohol
• Active infections such as but not limited to tuberculosis, cytomegalovirus, Epstein-Barr virus, herpes simplex, varicella zoster, viral hepatitis, toxoplasmosis, HIV or syphilis.
• Active malignancy or history of malignancy with the exception of local basal cell carcinoma or carcinoma in situ of the cervix

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment efficacy	The proportion of patients with ne evidence of disease activity-3 (NEDA-3) as defined by: no clinical relapse, no disability progression, no radiological disease activity.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual relapse rate		2 years
Time to first relapse		2 years
Confirmed disability progression (CDP)	Measured by the Expanded Disability Status Scale (EDSS) CDP-EDSS is defined as an increase of one point in the EDSS score from baseline to month 24.	2 years
Confirmed disability improvement (CDI)	Measured by the Expanded Disability Status Scale (EDSS) CDI-EDSS is defined as a decrease of one point in the EDSS score from baseline to month 24, with an absence of relapse at the point of assessment.	2 years
Progression independent of relapse activity (PIRA)	Defined as an episode of CDP without relapse during the 90 days before EDSS increase and during the 6-month period between the EDSS increase and the confirmation of disability progression.	2 years
Changes on the multiple sclerosis functional composite (MSFC)	MSFC consists of the timed 25-foot walk test, 9-hole peg test and standard digit modalities test (SDMT)	2 years
Brain/spinal cord MRI	Presence and number of contrast-enhancing lesions at baseline and the development of new or enlarging lesions between baseline and follow-up will be assessed.	2 years
Optical coherence tomography (OCT)	Developments of optic neuritis and longitudinal changes of the retinal nerve fiber layer will be assessed.	2 years
Side-effects and toxicity	Frequency and type of (serious) adverse events such as infections, secondary auto-immunity, fertility problems, clinical relevant changes on physical examination and use of concomitant medications will be assessed	2 years
Multiple Sclerosis Impact Scale-29 (MSIS-29)	Patient reported outcome measures about the impact of MS on daily life	2 years
EuroQoL 5D (EQ-5D-5L)	Patient reported outcome measures about quality of life	2 years
Modified Fatigue Impact Scale (MFIS-5)	Patient reported outcome measures about fatigue	2 years
Hospital Anxiety and Depression Scale (HADS)	Patient reported outcome measures about anxiety and depression	2 years
iMTA Medical Cost Questionnaire (iMCQ)	Patient reported outcome measures about medical consumption	2 years
iMTA Productivity Cost Questionnaire (iPCQ)	Patient reported outcome measures about productivity	2 years
Treatment Satisfaction Questionnaire for Medication (TSQM)	Patient reported outcome measures about medication	2 years
Biomarkers	Serum NfL and GFAP over time	2 years
Proteomics	Olink discover panel	2 years
Immune phenotyping	Characterization of innate and adaptive immune subsets with mass spectrometry imaging	2 years
Genetic analysis	Immune gene profiling for gene signatures predictive for response to aHSCT	2 years

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: St. Antonius Hospital
• Investigators: Principal Investigator: J. Killestein, MSc, PhD, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: NL83783.018.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No