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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Ms
Rachel
Glover
+44 (0)114 222 4265
r.e.glover@sheffield.ac.uk
Prof
John
Snowden
+44 (0)114 271 3357
john.snowden1@nhs.net
More information about this study, what is involved and how to take part can be found on the study website.
Relapsing-remitting multiple sclerosis
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Multiple sclerosis is a chronic autoimmune inflammatory disease of the central nervous system which leads to impairment in strength, sensation, balance, vision, cognition and sphincter function. Relapsing-remitting multiple sclerosis (RRMS) is a type of multiple sclerosis with flare-ups and periods of remission in between. For patients with highly active relapsing-remitting multiple sclerosis (RRMS), disease-modifying therapies are available but there is growing evidence that autologous haematopoietic stem cell transplantation (aHSCT) may be more effective in reducing relapse rates and improving disability and quality of life. The aim of this study is to compare aHSCT against the four most effective disease-modifying therapies currently
available in the UK, alemtuzumab, ocrelizumab, ofatumumab and cladribine.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
2024 Protocol article in https://pubmed.ncbi.nlm.nih.gov/38316583/ (added 06/02/2024)
You can take part if:
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.
*b. When assessing eligibility an objective assessment is preferred for inclusion in the trial. If an objective assessment is not available, a detailed narrative of the relapse can be considered by the central team during the eligibility assessment
*c. Two or more new/newly enlarging T2 lesions
*d. Defined as patients with two or more disabling relapses in 1 year, and with one or more gadolinium-enhancing lesions or a significant increase in T2 lesion load on brain MRI compared with a previous MRI
*e. When patients present with RES MS, and when first-line DMTs are failing to control patients’ disease before a full course of treatment has been completed and other interventions (such as repeated courses of steroids and plasma exchange) have been used but failed to control their illness, they are often referred to as “treatment naïve”. This group of patients with highly inflammatory disease, which is resisting and progressing despite initial trea
You may not be able to take part if:
Current exclusion criteria as of 07/10/2022:1. Diagnosis of primary or secondary progressive MS2. Disease duration of > 10 years from symptom onset (note: symptoms must be clearly attributable to MS)3. Previous use of alemtuzumab, ocrelizumab, ofatumumab or cladribine4. Previous HSCT for any reason, or any previous experimental or commercial stem cell therapy5. 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 infection7. Pregnant or breastfeeding females8. 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. Maleparticipants 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 sixmonths following discontinuation (i.e. the last dose) of cyclophosphamide or cladribine9. Unable to comply with treatment protocol10. Contraindication to the use of cyclophosphamide, G-CSF (filgrastim or lenograstim) or rabbit ATG11. Participants with significant medical co-morbidity that precludes aHSCT as assessed by the local haematology team12. Significant language barriers, which are likely to affect the participant’s understanding of the study, or the ability to complete outcome questionnaires13. Concurrent participation in another interventional clinical trial14. AST and ALT >2.5 x upper limit of normal (ULN), bilirubin > 1.5 x ULN or direct bilirubin >ULN for participants with total bilirubin levels >1.5 x ULN15. Current diagnosis of a clinically defined bleeding disorder (patients with platelet counts of 100x109/l or above up to normal range are not excluded, as per section 18d. Persistently abnormal coagulation tests should be addressed to determine whether they constitute a defined bleeding disorder)16. Diagnosis of a clinically defined autoimmune disorder other than multiple sclerosis. (i.e. meeting full current international clinical and laboratory criteria for a specific autoimmune disorder)17. Patients with a history of myocardial infarction, angina pectoris, stroke or arterial dissection18. Participants who are not considered medically fit for aHSCT defined by any of the following. Note that these criteria are not automatic exclusion criteria but if any of these criteria are met, and in the opinion of the PI the participant is medically fit enough to undergo aHSCT, the case may be put forward to the central team for discussion about eligibility:18.1. Renal: creatinine clearance < 40ml/min (measured or estimated)18.2. Cardiac: clinical evidence of refractory congestive heart failure, left ventricular ejection fraction < 45% by cardiac echo; uncontrolled ventricular arrhythmia; pericardial effusion with haemodynamic consequences as evaluated by an experienced echocardiographer18.3. Concurrent neoplasms or myelodysplasia18.4. Bone marrow insufficiency defined as neutropenia with an absolute neutrophil count < 1x109/l, or thrombocytopenia with a platelet count < 100x109/l, or anaemia with a haemoglobin < 100g/l18.5. Diagnosis of hypertension, which is uncontrolled despite at least two antihypertensive agents18.6. Uncontrolled acute or chronic infection with any infection the investigator or central team consider a contraindication to participation. (N.B. Baseline JC virus serology will be recorded, but positivity will not be an exclusion criterion)18.7. Other chronic disease-causing significant organ failure, including established cirrhosis with evidence of impaired synthetic function on biochemical testing. This also includes known respiratory disease which, in the opinion of the local haematologist would represent a significant risk to the safe administration of aHSCT. Patients for whom there is concern about potential respiratory disease must undergo a formal evaluation by a respiratory physician, including pulmonary function and blood gas measurement
Previous exclusion criteria:1. Diagnosis of primary or secondary progressive MS2. Disease duration of > 10 years from symptom onset (note: symptoms must be clearly attributable to MS)3. Previous use of alemtuzumab, ocrelizumab or cladribine4. Previous HSCT for any reason, or any previous experimental or commercial stem cell therapy5. 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 infection7. Pregnant or breastfeeding females8. 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. Male participants with female partners of child-bearing potential must use adequate contraception if they are randomised to the aHSCT arm during treatment and for at least six months following discontinuation (i.e. the last dose) of cyclophosphamide9. Unable to comply with treatment protocol10. Contraindication to the use of cyclophosphamide, G-CSF (filgrastim or lenograstim) or rabbit ATG11. Participants with significant medical co-morbidity that precludes aHSCT as assessed by the local haematology team12. Significant language barriers, which are likely to affect the participant’s understanding of the study, or the ability to complete outcome questionnaires13. Concurrent participation in another interventional clinical trial14. AST and ALT >2.5 x upper limit of normal (ULN), bilirubin > 1.5 x ULN or direct bilirubin >ULN for participants with total bilirubin levels >1.5 x ULN15. Current diagnosis of a clinically defined bleeding disorder (patients with platelet counts of 100x109/l or above up to normal range are not excluded, as per section 18d. Persistently abnormal coagulation tests should be addressed to determine whether they constitute a defined bleeding disorder)16. Diagnosis of a clinically defined autoimmune disorder other than multiple sclerosis. (i.e. meeting full current international clinical and laboratory criteria for a specific autoimmune disorder)17. Patients with a history of myocardial infarction, angina pectoris, stroke or arterial dissection18. Participants who are not considered medically fit for aHSCT defined by any of the following. Note that these criteria are not automatic exclusion criteria but if any of these criteria are met, and in the opinion of the PI the participant is medically fit enough to undergo aHSCT, the case may be put forward to the central team for discussion about eligibility:18.1. Renal: creatinine clearance < 40ml/min (measured or estimated)18.2. Cardiac: clinical evidence of refractory congestive heart failure, left ventricular ejection fraction < 45% by cardiac echo; uncontrolled ventricular arrhythmia; pericardial effusion with haemodynamic consequences as evaluated by an experienced echocardiographer18.3. Concurrent neoplasms or myelodysplasia18.4. Bone marrow insufficiency defined as neutropenia with an absolute neutrophil count < 1x109/l, or thrombocytopenia with a platelet count < 100x109/l, or anaemia with a haemoglobin < 100g/l18.5. Diagnosis of hypertension, which is uncontrolled despite at least two antihypertensive agents18.6. Uncontrolled acute or chronic infection with any infection the investigator or central team consider a contraindication to participation. (N.B. Baseline JC virus serology will be recorded, but positivity will not be an exclusion criterion)18.7. Other chronic disease-causing significant organ failure, including established cirrhosis with evidence of impaired synthetic function on biochemical testing. This also includes known respiratory disease which, in the opinion of the local haematologist would represent a significant risk to the safe administration of aHSCT. Patients for whom there is concern about potential respiratory disease must undergo a formal evaluation by a respiratory physician, including pulmonary function and blood gas measurement
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Prof
John
Snowden
+44 (0)114 271 3357
john.snowden1@nhs.net
Ms
Rachel
Glover
+44 (0)114 222 4265
r.e.glover@sheffield.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
The study is sponsored by Sheffield Teaching Hospitals NHS Foundation Trust and funded by NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/126/26.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 44920
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