A multicentre, randomised controlled trial to evaluate the efficacy of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing-remitting multiple sclerosis

Overview

2024 Protocol article in https://pubmed.ncbi.nlm.nih.gov/38316583/ (added 06/02/2024)

Registry

who.int

Start Date

September 9, 2020

End Date

May 31, 2026

Last Updated

last year

Study Type

Interventional

Sex

All

Sponsor

•Current inclusion criteria as of 07/10/2022:
•1\. Diagnosis of MS using the 2017 McDonald criteria
•2\. Age 16\-55 years inclusive
•3\. EDSS 0\-6\.0 inclusive\*a. If the EDSS score is 6\.0 this must be due to confirmed relapse rather than progressive disease
•4\. Severe inflammatory disease defined as RRMS course with 1 or more protocol\-defined relapses\*b, or evidence of MRI disease activity\*c in the last 12 months (at the time of screening) despite being on a DMT, or rapidly evolving severe MS\*d in treatment naïve patients\*e
•5\. Clinical stability for \>30 days following last relapse at the time of screening
•6\. Participants who have been reviewed by the central neurology team and confirmed as eligible
•7\. Participants who, in the opinion of the local haematology lead or delegate, are fit enough to undergo treatment.
•8\. Able to undergo MRI examination
•\*a. Patients with EDSS scores of 0\-1\.5 must also fulfil the following criteria: short illness duration (\<5 years), active disease clinically and radiologically (i.e., at least 2 relapses in the last 12 months and evidence of multiple Gad\-enhancing MRI lesion), high brain lesion load and brain or spinal cord atrophy.

•Current exclusion criteria as of 07/10/2022:
•1\. Diagnosis of primary or secondary progressive MS
•2\. Disease duration of \> 10 years from symptom onset (note: symptoms must be clearly attributable to MS)
•3\. Previous use of alemtuzumab, ocrelizumab, ofatumumab or cladribine
•4\. Previous HSCT for any reason, or any previous experimental or commercial stem cell therapy
•5\. JCV antibody Index of \> 1\.5 in patients previously treated with natalizumab (unless they are CSF JCV PCR negative)
•6\. Prior diagnosis of Hepatitis B, Hepatitis C or HIV infection or current TB infection
•7\. Pregnant or breastfeeding females
•8\. Unwilling to use adequate contraception during the trial. Female participants of child\-bearing potential must use adequate contraception for the duration of the trial (24 months), and for 12 months after discontinuation of cyclophosphamide or ocrelizumab, or 4 months after the last dose of alemtuzumab, or 6 months after the last dose of cladribine or ofatumumab. Male
•participants with female partners of child\-bearing potential must use adequate contraception if they are randomised to the aHSCT arm or cladribine during treatment and for at least six