ISRCTN88667898进行中（未招募）未知
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
适应症
试验速览
- 阶段
- 未知
- 状态
- 进行中（未招募）
- 入组人数
- 198
研究概览
简要总结
2024 Protocol article in https://pubmed.ncbi.nlm.nih.gov/38316583/ (added 06/02/2024)
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •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 treatments, have a poor long-term prognosis.
- •Previous inclusion criteria from 26/01/2021 to 07/10/2022:
- •1. Diagnosis of MS using the 2017 McDonald criteria
- •2. Age 16-55 years inclusive
- •3. EDSS 0-6.0 inclusive*. 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 2 or more protocol-defined relapses, or 1 such relapse and evidence of MRI disease activity > 3 months before or after its onset, in the last 12 months despite being on a DMT*
- •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
- •*Patients with EDSS scores of 0-1.5 or those who failed only first-line treatments 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
- •Previous inclusion criteria:
- •1. Diagnosis of MS using the 2017 McDonald criteria
- •2. Age 16-55 years inclusive
- •3. EDSS 0-6.0 inclusive*. If the EDSS
排除标准
- •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
- •months following discontinuation (i.e. the last dose) of cyclophosphamide or cladribine
- •9. Unable to comply with treatment protocol
- •10. Contraindication to the use of cyclophosphamide, G-CSF (filgrastim or lenograstim) or rabbit ATG
- •11. Participants with significant medical co-morbidity that precludes aHSCT as assessed by the local haematology team
- •12. Significant language barriers, which are likely to affect the participant’s understanding of the study, or the ability to complete outcome questionnaires
- •13. Concurrent participation in another interventional clinical trial
- •14. 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 ULN
- •15. 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 dissection
- •18. 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 echocardiographer
- •18.3. Concurrent neoplasms or myelodysplasia
- •18.4. 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/l
- •18.5. Diagnosis of hypertension, which is uncontrolled d
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