Randomized Autologous heMatopoietic stem cell transplantation versus alemtuzumab, cladribine or ocrelizumab for patients with relapsing remitting Multiple Sclerosis
- Conditions
- MSMultiple sclerosis10012303
- Registration Number
- NL-OMON52451
- Lead Sponsor
- Helse Bergen HF, Haukeland University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
1. Diagnosis of RRMS using revised McDonald criteria of clinically definite MS
2. Age between > 18 to <50, both genders
3. An EDSS score of 0 to 5.5
4. 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:
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 occurred 3 or more months after the onset of an
immunomodulatory treatment
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, 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 mitoxantrone,
alemtuzumab, cladribin and ocrelizumab, and treatment with rituximab within the
last 9 months prior to start of study treatment.
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 (UNL)
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 heredit
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint of this prospective, randomized study is to<br /><br>determine differences between patients in the 2 treatment arms according to the<br /><br>following criteria:<br /><br>• Study Part I: Proportion of patients with no evidence of disease activity<br /><br>(NEDA, as defined per protocol) during a 2 year (96 week) period<br /><br>• Study Part II: Proportion of patients with NEDA (as defined per protocol)<br /><br>during a 5 year (240 week) period.</p><br>
- Secondary Outcome Measures
Name Time Method