None listed
Conditions
Brief summary
Executive Summary Alemtuzumab is a highly effective treatment for multiple sclerosis which has been demonstrated by three major clinical trials. However there are significant safety concerns arising from both the nature of the treatment and the results of the clinical trials. The principal risk is the late development of other treatable autoimmune diseases, such as immune thrombocytopenia. It is likely that by monitoring treated patients with regular blood tests, including monthly platelet counts, patients who develop such autoimmune diseases can be identified and potentially treated in some cases before catastrophic clinical sequelae occur. The risk of treatment with alemtuzumab will be thereby mitigated. However current real world (off-trial) clinical systems for ensuring patients actually get monthly blood tests and that the results are checked for early deviations from the norm are not adequate. This study proposes the development of a semi-automated Clinical Decision Support System (CDSS) using international IT pathology standards that checks for the presence of results, analyses the results and determines the need for automated or human alerts as required. Another risk is that associated with the immunosuppression and the attendant increase in infections and to a lesser extent certain malignancies. Fortunately in the trials this has not been a major problem other than herpes simplex virus which required a trial amendment for prophylaxis. However the trials did not include patients with prior immunosuppressive MS treatment which will occur in the real world. This study proposes the qualitative comparison of a specific patient education module and a standardized risk assessment module extended safety screening system to the procedures used in the CAMMS protocol. The aim of this study is to develop systems that help mitigate the risk associated with use of alemtuzumab and thereby improve the relationship between benefit and risk from this medication. It is proposed that this study be commenced and the systems developed now as the study anticipates potential regulatory concerns and the systems proposed may help in addressing regulatory concerns and in mitigating post regulatory approval risks of treatment.
Interventions
A two year observational study of open label treatment with alemtuzumab for multiple sclerosis (MS). The aim of the study is to develop efficient information-technology (IT) based methods for the monthly monitoring required by the risk management protocols after treatment with alemtuzumab. The effectiveness of alemtuzumab in MS has already been demonstrated in randomised trials and is not the subject of this study.
Normally after treatment of MS with alemtuzumab patients are required to have o
A two year observational study of open label treatment with alemtuzumab for multiple sclerosis (MS). The aim of the study is to develop efficient information-technology (IT) based methods for the monthly monitoring required by the risk management protocols after treatment with alemtuzumab. The effectiveness of alemtuzumab in MS has already been demonstrated in randomised trials and is not the subject of this study. Normally after treatment of MS with alemtuzumab patients are required to have ongoing monthly pathology monitoring. The study is to test the successful development of an electronic semi-automated monitoring of pathology results. There is no additional involvement for participants other than the normal monthly pathology testing per alemtuzumab treatment protocol.
Sponsors
Sydney Local Health District
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing to provide informed consent to both treatment with alemtuzumab and inclusion in the PRIME clinical decision support system monitoring procedures 2. Age 18 or older as of the date the consent is signed 3. Definite relapsing remitting MS by McDonald 2010 criteria 4. Cranial MRI scan demonstrating white matter lesions attributable to MS within 1 year of Screening 5. Active MS as signified by at least 2 relapses in the last 2 years and at least 1 relapse in the last 1 year 6. Either: a. Failure of first line disease-modifying treatment as determined by: at least 1 relapse of MS despite treatment with a TGA-approved treatment for MS (interferons, glatiramer, teriflunomide, fingolimod or natalizumab), or at least 1 relapse in a patient unable to be treated with TGA-approved MS treatments due to intolerance or unacceptable risks of these treatments b. Previously untreated MS that is associated with at least one gadolinium enhancing lesion on MRI in the last 1 year. 7. Diagnosed disease duration <= 10years 8. Baseline EDSS 0 – 4.0
Exclusion criteria
a. As per CAMMS03409 amendment 2: i. Does not wish to receive alemtuzumab ii. Ongoing participation in any other investigational study iii. Has received alemtuzumab off-label iv. Known bleeding disorder (eg, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency) or therapeutic anticoagulation v. Diagnosis of immune thrombocytopenic purpura (ITP), or other autoimmune hematologic abnormality. vi. History of malignancy, except basal cell skin carcinoma vii. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis viii. Significant non-MS autoimmune disease including but not limited to: immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis, or anti-glomerular basement membrane disease (anti-GBM disease, also known as Goodpasture’s disease) ix. Major psychiatric disorder or epileptic seizures not adequately controlled by treatment x. Known infection with hepatitis B or C virus, seropositivity for human immunodeficiency virus (HIV). xi. History of invasive fungal infections xii. Unwilling to agree to use a reliable and acceptable contraceptive method for at least 6 months following each alemtuzumab treatment cycle (fertile patients only). Reliable and effective contraceptive method(s) include: intrauterine device (IUD), hormonal-based contraception, surgical sterilization, abstinence or double-barrier contraception (condom and occlusive cap [diaphragm or cervical cap with spermicide]) b. Plus (local exclusion criteria) i. Not resident in NSW ii. Not able to access Douglass Hanly Moir pathology services iii. Not able or likely to fulfil the requirements of the study for any other reason iv. Not able to access electronic reminders and alerts (patient must have both a mobile (cell) phone and a valid regularly checked email address, the patient’s designate person must have at least one of these two methods of contact, prefer both) v. Allergic or intolerant of any agent required for the completion of this study (i.e alemtuzumab, gadolinium contrast) vi. No history of primary infection or vaccination with varicella zoster virus, until vaccinated vii. Other significant active or latent infection until treated viii. Any other reason that an investigator regards as a contraindication to entering or ability to complete the study c. The following are not exclusion criteria but caution should be exercised in including patients with these criteria noting that these were exclusion criteria for the alemtuzumab RCTs i. Prior exposure to natalizumab, fingolimod, mitoxantrone, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent ii. Patients > 50 years of age iii. Disease duration 5-10 years after diagnosis iv. EDSS 3.5-4 v. Patients with known thyroid autoimmunity or thyroid antibodies. Such patients are highly likely to develop clinical thyroid autoimmunity and this should be discussed with the patient.
Outcome results
None listed