Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden

NCT05029206 | Completed

• 1 other identifier: EPM 2021-01530
• Study Type: observational
• Target: 174
• Locations: 1 country
• Sites: 8

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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Keywords

Autologous hematopoietic stem cell transplantation; Chemotherapy; Cyclophosphamide; Etoposide; Carmustine; Cytarabine; Melphalan; Antilymphocyte serum

Outcome Measures

Primary Outcomes (2)

• No evidence of disease activity (NEDA)

  NEDA is defined as absence of relapses in addition to absence of clinical progression and MRI progression.

  5 years

• Treatment related mortality (TRM)

  TRM is defined as death due to any transplantation-related cause other than disease progression.

  Up to 18 years

Secondary Outcomes (9)

• No evidence of disease activity (NEDA)

  3 years and 10 years

• MRI event free survival

  At 3, 5 and 10 years

• Relapse free survival

  At 3, 5 and 10 years

• Progression free survival

  At 3, 5 and 10 years

• Annualized relapse rate (ARR)

  Up to 17 years

Other Outcomes (3)

• Changes in cognitive function

  At 1, 2 and 3 years

• Changes in quality of life

  At 1, 2 and 3 years

• Changes in MS-related fatigue

  At 1, 2 and 3 years

Interventions

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. 1. In Sweden, the mobilization of HSCs has been made by a combination of cyclophosphamide (2 g/m2) and granulocyte-colony-stimulating factor. 2. A minimum of 2 × 10\^6 CD34+ cells/kg is harvested and cryopreserved. No in vitro manipulation is done to the stem cells. 3. 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. 4. After a minimum of 24 hours after the last administration of chemotherapy have passed, the reinfusion of autologous CD34+ cells is performed.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (8)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Skåne University Hospital

Lund, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Danderyd Hospital

Stockholm, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Umeå University Hospital

Umeå, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

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MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Joachim Burman, MD, PhD

  Uppsala University

  PRINCIPAL INVESTIGATOR

• Thomas Silfverberg, MD

  Uppsala University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: August 31, 2021
• Study Start: May 5, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The data set will be stored for 15 years
• 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.

Locations

SE (8)