Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden (AutoMS-Swe)

November 21, 2023 updated by: Uppsala University

Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden - a Register-based Retrospective Observational Study

This is an observational cohort study with retrospective analysis of prospectively collected data. The study cohort is constituted of all patients with relapsing-remitting multiple sclerosis (RRMS) treated with autologous stem cell transplantation (AHSCT) in Sweden from 2004 when the first AHSCT was performed until 31 December 2019. The study aims to describe the effectiveness, safety and patient reported outcomes of AHSCT for MS through real world data. Treatment related mortality will be analyzed from start of mobilization until the end of the study. For other adverse events the data collection will end 3 months post-transplantation. A statistical subgroup comparison of efficacy and safety between the conditioning regimens BEAM-ATG and Cy-ATG will be included within the study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

All individuals with a diagnosis of MS, who was treated with AHSCT in Sweden until 31 December 2019 can be included in this study. Patients will be identified through the European Bone and Marrow Transplantation register (EBMT) and the Swedish MS register (SMSreg).

Baseline data will be collected from the SMSreg. Data concerning AHSCT will be collected from local repositories of the EBMT and supplemented by data obtained by reviewing of medical records. This includes data such as doses and names of drugs used for mobilization and conditioning, dates for administration of these drugs, date of hematopoietic stem cell transplantation, date of hematological milestones, occurrence and grading of adverse events during the first three months after the intervention.

Data on clinical outcome after the first three months of the intervention will be collected from SMSreg. Data on vital status will be collected from medical records at the end of study. Any recorded deaths will be analyzed through the medical records to determine if it was treatment-related.

The endpoints will be analysed and described for the whole study cohort. A subgroup analysis comparing the outcome of patients treated with different conditioning regimens (e.g. BEAM-ATG and Cy-ATG) will be included in this study.

Study Type

Observational

Enrollment (Actual)

174

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Gothenburg, Sweden
        • Sahlgrenska University Hospital
      • Linköping, Sweden
        • Linkoping University Hospital
      • Lund, Sweden
        • Skane University Hospital
      • Stockholm, Sweden
        • Karolinska University Hospital
      • Stockholm, Sweden
        • Danderyd Hospital
      • Umeå, Sweden
        • Umea University Hospital
      • Uppsala, Sweden
        • Uppsala University Hospital
      • Örebro, Sweden
        • Orebro University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

All individuals with a diagnosis of MS, who was treated with AHSCT in Sweden until December 31st 2019 can be included in this study.

Description

Inclusion Criteria:

  • Diagnosis of multiple sclerosis according to the revised McDonald criteria 2017.
  • Autologous hematopoietic stem cell transplantation performed for treating multiple sclerosis at a Swedish transplantation center until December 31st 2019.

Exclusion Criteria:

  • Diagnosis of primary progressive MS or secondary progressive MS according to Lublin et al at the time of transplantation.
  • Patient not accepted reporting of data to the EBMT register.
  • Not fulfilling requirements of the minimal dataset, se below.

Definition of minimal dataset

  • Data on disease course of multiple sclerosis at the time of transplantation.
  • Transplantation and the following in-patient care performed in Sweden.
  • Date of transplantation.
  • Data on drugs used in conditioning.

  • At least one follow-up visit performed in Sweden (unless early death before first follow-up visit) including data on:

    • Clinical assessment
    • The Kurtzke Expanded Disability Status Scores (EDSS)

Additional note: For a patient to be included in the analysis of treatment effectiveness data on MRI evaluation is needed at least once during follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
No evidence of disease activity (NEDA)
Time Frame: 5 years
NEDA is defined as absence of relapses in addition to absence of clinical progression and MRI progression.
5 years
Treatment related mortality (TRM)
Time Frame: Up to 18 years
TRM is defined as death due to any transplantation-related cause other than disease progression.
Up to 18 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
No evidence of disease activity (NEDA)
Time Frame: 3 years and 10 years
NEDA is defined as absence of relapses in addition to absence of clinical progression and MRI progression.
3 years and 10 years
MRI event free survival
Time Frame: At 3, 5 and 10 years
The appearance of any T2 lesion > 3 mm or gadolinium enhancing lesion in the brain or spinal cord not present on the baseline scan measured from the time of AHSCT.
At 3, 5 and 10 years
Relapse free survival
Time Frame: At 3, 5 and 10 years
A clinical relapse defined as a period of acute worsening of neurological function lasting ≥ 24 hours not attributable to an external cause such as increased body temperature or acute infection, measured from the time of AHSCT.
At 3, 5 and 10 years
Progression free survival
Time Frame: At 3, 5 and 10 years

The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis. The EDSS is a composite of disability in eight functional systems.

Baseline EDSS ≤ 5 An increase in EDSS score with at least 1 point from baseline that is sustained between two follow-up visits separated in time by no less than six months.

Baseline EDSS ≥ 5.5 An increase in EDSS score with at least 0.5 points from baseline that is sustained between two follow-up visits separated in time by no less than six months.
At 3, 5 and 10 years
Annualized relapse rate (ARR)
Time Frame: Up to 17 years
The number of relapses occurring during a time period divided by the number of years in that time period. E.g. 5 relapses occurring in a time period of 2.5 years equals an ARR of 2 (5/2.5=2), after AHSCT.
Up to 17 years
Proportion of patients with clinical improvement
Time Frame: Up to 17 years

The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis. The EDSS is a composite of disability in eight functional systems.

Baseline EDSS ≤ 5.5 A decrease in EDSS score with at least 1 point from baseline that is sustained between two follow-up visits separated in time by no less than six months.

Baseline EDSS ≥ 6 A decrease in EDSS score with at least 0.5 points from baseline that is sustained between two follow-up visits separated in time by no less than six months.
Up to 17 years
EDSS change
Time Frame: At 1, 2 and 3 years

The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis. The EDSS is a composite of disability in eight functional systems.

Any change in EDSS from baseline to follow-up.
At 1, 2 and 3 years
Grade 3 serious adverse events the first 100 days
Time Frame: 100 days
The frequency and of grade 3 serious adverse events within 100 days as defined by the NIH common terminology criteria for adverse events (CTCAE).
100 days
Grade 4 serious adverse events the first 100 days
Time Frame: 100 days
The frequency and of grade 3 serious adverse events within 100 days as defined by the NIH common terminology criteria for adverse events (CTCAE).
100 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in cognitive function
Time Frame: At 1, 2 and 3 years
Explorative outcome. Measured by Symbol Digit Modalities Test (SDMT) is a test of cognitive function in MS-patients.
At 1, 2 and 3 years
Changes in quality of life
Time Frame: At 1, 2 and 3 years
Explorative outcome. Changes in quality of life, measured by the Multiple Sclerosis Impact Scale (MSIS-29) from the patient's perspective.
At 1, 2 and 3 years
Changes in MS-related fatigue
Time Frame: At 1, 2 and 3 years
Explorative outcome. As measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC), a 20-item scale for evaluating MS-related cognitive and motor fatigue.
At 1, 2 and 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Uppsala University

Collaborators

Karolinska University Hospital
Sahlgrenska University Hospital, Sweden
University Hospital, Linkoeping
Skane University Hospital
University Hospital, Umeå
Region Örebro County
Uppsala University Hospital

Investigators

  • Principal Investigator: Joachim Burman, MD, PhD, Uppsala University
  • Study Chair: Thomas Silfverberg, MD, Uppsala University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2021

Primary Completion (Actual)

September 30, 2022

Study Completion (Actual)

September 30, 2022

Study Registration Dates

First Submitted

June 9, 2021

First Submitted That Met QC Criteria

August 25, 2021

First Posted (Actual)

August 31, 2021

Study Record Updates

Last Update Posted (Estimated)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 21, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPM 2021-01530

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study protocol will be made available upon request.

IPD Sharing Time Frame

The data set will be stored for 15 years

IPD Sharing Access Criteria

Study protocol will be made available upon request. Access to study data will be decided after contact with the study principal investigator. All access should be of scientific purposes.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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