Assessing the Induction of Long-term Immune Regulation Following Treatment With Lemtrada® (Alemtuzumab).

Study Overview
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Brief Summary
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In this study the investigators wish to test the hypothesis that treatment with Lemtrada is associated with alterations in immune homeostasis in favor of multiple regulatory leukocyte populations which persist long after completion of the treatment phase. Specifically, the investigators propose that regulatory B-cells are induced rapidly following the first course of treatment with Lemtrada, that this occurs prior to induction of other regulatory populations, and that these cells are functionally capable of regulating immune responses. The investigators also propose that there is a concomitant induction of functional regulatory T-cells and alternatively-activated monocytes during the first year after treatment giving a blanket enhanced regulatory immune profile. This study is designed primarily to identify possible mechanisms by which Lemtrada acts to modify the immune environment in recipient patients, as such the outcome measures are all immunological.

Official Title
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Assessing the Induction of Long-term Immune Regulation Following Treatment With Lemtrada® (Alemtuzumab).

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Assessment of leukocyte function.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must qualify to receive treatment with Lemtrada according to the USC, Department of Neurology, MS Group Clinical Lemtrada Protocol. Patient must have been diagnosed with clinically definite Multiple Sclerosis defined by the revised McDonald criteria (Polman et al., 2005, Polman et al., 2010) of the relapsing-remitting form with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5. Patient must have the ability to understand and sign this study-specific IRB-approved informed consent form. Patients must be willing to donate 80mls of blood for immunological testing either prior to receiving Lemtrada or 6, 12, 18 or 24 months after first round of treatment. Exclusion Criteria: Patient does not qualify to receive treatment with Lemtrada according to the USC, Department of Neurology, MS Group Clinical Lemtrada Protocol. Inability to understand nature of the study. Patient has any form of progressive MS. Patient has been diagnosed with any other autoimmune disease. Patient is of child bearing age with a positive pregnancy test or is unwilling to agree to use a reliable contraceptive method. Treatment with any of the following within 30 days of commencing treatment with Lemtrada or collection of baseline blood sample: Gilenya, Aubagio, Tecfidera. Treatment with Natalizumab within 60 days of commencing treatment with Lemtrada or collection of baseline blood sample. Treatment with any of the following within 6 months of commencing treatment with Lemtrada or collection of baseline blood sample: Rituximab, Ocrevus. Treatment at any time with any of the following: Mitoxantrone, Cyclophosphamide, Cladribine, Cyclosporine, Azathioprine, Methotrexate or any other immunomodulatory, immunosuppressant or immune homeostasis altering drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lemtrada treated - 6 month<br>Patients that received their first course of treatment with Lemtrada approximately 6 months prior. | Other: Assessment of leukocyte function.<br>* The function and phenotype of regulatory B-cells, regulatory T-cells and alternatively-activated monocytes will be assessed directly ex vivo from PBMC.<br>|
| Lemtrada treated - 12 month<br>Patients that received their first course of treatment with Lemtrada approximately 12 months prior but who have not received the second course of treatment. | Other: Assessment of leukocyte function.<br>* The function and phenotype of regulatory B-cells, regulatory T-cells and alternatively-activated monocytes will be assessed directly ex vivo from PBMC.<br>|
| Lemtrada treated - 18 month<br>Patients that received their first course of treatment with Lemtrada approximately 18 months prior and their second course of treatment with Lemtrada approximately 6 months prior. | Other: Assessment of leukocyte function.<br>* The function and phenotype of regulatory B-cells, regulatory T-cells and alternatively-activated monocytes will be assessed directly ex vivo from PBMC.<br>|
| Lemtrada treated - 24 month<br>Patients that received their first course of treatment with Lemtrada approximately 24 months prior and their second course of treatment with Lemtrada approximately 18 months prior and who have not received any further treatment. | Other: Assessment of leukocyte function.<br>* The function and phenotype of regulatory B-cells, regulatory T-cells and alternatively-activated monocytes will be assessed directly ex vivo from PBMC.<br>|
| Lemtrada qualified - untreated<br>Patients that are qualified to start treatment with Lemtrada but have not yet being untreated. | Other: Assessment of leukocyte function.<br>* The function and phenotype of regulatory B-cells, regulatory T-cells and alternatively-activated monocytes will be assessed directly ex vivo from PBMC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess changes in the circulating regulatory B-cell population. |  | 12 months |