Clinical trial NCT05029206: Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden
Official title: Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden - a Register-based Retrospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Keywords: Autologous hematopoietic stem cell transplantation
Chemotherapy
Cyclophosphamide
Etoposide
Carmustine
Cytarabine
Melphalan
Antilymphocyte serum
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
name: Sahlgrenska University Hospital
name: Uppsala University Hospital
name: Skane University Hospital
name: University Hospital, Linkoeping
name: University Hospital, Umeå
name: Region Örebro County
First posted: 2021-08-31
Enrollment: 174
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: No evidence of disease activity (NEDA)
timeFrame: 5 years
measure: Treatment related mortality (TRM)
timeFrame: Up to 18 years
Secondary outcomes:
measure: No evidence of disease activity (NEDA)
timeFrame: 3 years and 10 years
measure: MRI event free survival
timeFrame: At 3, 5 and 10 years
measure: Relapse free survival
timeFrame: At 3, 5 and 10 years
measure: Progression free survival
timeFrame: At 3, 5 and 10 years
measure: Annualized relapse rate (ARR)
timeFrame: Up to 17 years
measure: Proportion of patients with clinical improvement
timeFrame: Up to 17 years
measure: EDSS change
timeFrame: At 1, 2 and 3 years
measure: Grade 3 serious adverse events the first 100 days
timeFrame: 100 days
measure: Grade 4 serious adverse events the first 100 days
timeFrame: 100 days
Other outcomes:
measure: Changes in cognitive function
timeFrame: At 1, 2 and 3 years
measure: Changes in quality of life
timeFrame: At 1, 2 and 3 years
measure: Changes in MS-related fatigue
timeFrame: At 1, 2 and 3 years
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Danderyd Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Uppsala University
name: Joachim Burman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uppsala University
name: Thomas Silfverberg, MD
role: STUDY_CHAIR
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