Randomized study with stem cell transplantation versus standard treatment with alemtuzumab, cladribine or ocrelizumab in patients with relapsing remitting multiple sclerosis.
- Conditions
- Relapsing remitting multiple sclerosis.MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2017-001362-25-NL
- Lead Sponsor
- Helse Bergen HF, Haukeland University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Age between =18 to =50, both genders
2. Women of childbearing potential* (WOCBP) and men in a sexual relation with WOCBP must be ready and able to use highly effective methods of birth control¥ per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly for the duration of the study OR until 4, 6 and 12 months after last dose administered for alemtuzumab, cladribine or ocrelizumab respectively (the longest alternative applies). If treated with cladribine, women must use double barrier method during each treatment course and until 4 weeks after last dose in each treatment course is administered.
3. Diagnosis of RRMS using revised McDonald criteria of clinically definite MS1
4. An EDSS score of 0 to 5.5
5. Significant inflammatory disease activity in the last year despite treatment with standard disease modifying therapy (interferon beta, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, natalizumab)
a. Significant inflammatory disease activity is defined by:
i. One or more clinically reported multiple sclerosis (MS) relapse(s),
ii. AND 1 or more T1 Gd-enhanced lesion(s),
iii. OR three or more new or enlarging T2 lesions on magnetic resonance imaging (MRI)
The relapse(s) must have been treated with iv or oral high dose corticosteroids prescribed by a neurologist, and must have occurred 3 or more months after the onset of an immunomodulatory treatment, as MS immunomodulatory treatment may reach full effect after 3 months or more2.
6. The patient is a RRMS-patient referred from neurological departments in Norway, Denmark, Sweden, the Netherlands (or potentially from other countries participating in the study), to an assigned study site.
7. Signed informed consent and expected patient cooperation regarding the treatment schemes and procedures planned in the treatment and follow-up periods must be obtained and documented according to ICH GCP and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
1.Known hypersensitivity or other known serious side effects for any of the study medications, including co-medications such as high-dose glucocorticosteroids
2.Any illness or prior treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy or high-dose glucocorticosteroids
3.Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HTV, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity verified at Visit 1
4.Patients without a history of chickenpox or without vaccination against varicella zoster virus (VZV), unless tested for antibodies to VZV. VZV negative patients can only be included if they receive vaccination against VZV at least 6 weeks prior to inclusion.
5.Current or previous treatments with long-term effects that may influence the treatment effects or potential toxicities/side effects of the treatment arms. This includes, but is not restricted to previous treatment with rituximab, mitoxantrone, alemtuzumab, cladribin and ocrelizumab
6.Treatment with glucocorticoids or ACTH within one month prior to start of study treatment
7.Having experienced an MS relapse within one month prior to study inclusion
8.Prior or current major depression
9.Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
10.Prior or current alcohol or drug dependencies
11.Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhytmia, unstable or advanced ischemic heart disease (NYHA III or IV)
12.Significant hypertension: BP > 180/110
13.Active malignancy or prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix.
14.Known untreated or unregulated thyroid disease
15.Failure to willingly accept or comprehend risk of irreversible sterility as a side effect of therapy
16.WBC < 1,5 x 109/L if not caused by a reversible effect of documented ongoing medication. If WBC < 1,5 x 109/L is caused by a reversible effect of documented ongoing medication the WBC count must be > 1,5 x 109/L before start of study treatment.
17.Platelet (thrombocyte) count < 100 x 109/L
18.ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN)
19.Serum creatinine > 200 µmol/L
20.Serum bilirubin > ULN
21.Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams
22.Diagnosis of primary progressive MS
23.Diagnosis of secondary progressive MS
24.Treatment with natalizumab and fingolimod within the last 2 months, and treatment with dimetylfumurat within the last month (washout must be performed as specified in section 5.1) prior to start of study medication.
25.Use of teriflunomide (Aubagio®) within the previous 2 years unless cleared from the body (plasma concentration < 0.02 mcg/ml following elimination from the body with cholestyramine or activated powdered charcoal) as specified in section 5.1 prior to start of study medication.
26.Any hereditary neurological disease such as Charcot-Marie-Tooth disease or Spinocerebellar ataxia
27.Any disease that can influence the patient safety and compliance, or the evaluation of disability
28.History of hypersensitivity reaction to rab
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method