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NCT Number: NCT05029206

Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden

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.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

Sahlgrenska University Hospital, Gothenburg, Sweden

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

autologous hematopoietic stem cell transplantation

Procedure

The therapeutic intervention of AHSCT consists of four parts: the mobilization of hematopoietic stem cells (HSC), the harvest of HSC, the ablation (conditioning) of the immune system and the reinfusion of autologous HSCs.

  • In Sweden, the mobilization of HSCs has been made by a combination of cyclophosphamide (2 g/m2) and granulocyte-colony-stimulating factor.
  • A minimum of 2 × 10^6 CD34+ cells/kg is harvested and cryopreserved. No in vitro manipulation is done to the stem cells.
  • Two conditioning regimens have been used in Sweden for ablation. The BEAM-ATG protocol include carmustine (BCNU) 300 mg/m2, etoposide 800 mg/m2, cytarabine arabinoside (ARA-C) 800 mg/m2 and melphalan 140 mg/m2 + rATG or hATG. The Cy-ATG protocol include cyclophosphamide 200 mg/kg + rATG/hATG with 1000 mg Metylprednisolone given day -5 to -1.
  • After a minimum of 24 hours after the last administration of chemotherapy have passed, the reinfusion of autologous CD34+ cells is performed.

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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).

  9. 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).

Other outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

Uppsala University

Other

Collaborators

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

Registry information

Official study title

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

Acronym: AutoMS-Swe

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Aug 31, 2021
Registry last updated
Nov 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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