Clinical trial NCT03647722: Assessing the Induction of Long-term Immune Regulation Following Treatment With Lemtrada® (Alemtuzumab).
Official title: Assessing the Induction of Long-term Immune Regulation Following Treatment With Lemtrada® (Alemtuzumab).
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Multiple Sclerosis
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2018-08-27
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We will recruit 125 individuals with clinically definite MS, defined by the revised McDonald criteria (35). Patients in each cohort will be enrolled from those currently being seen by physicians at the University of Southern California, Department of Neurology.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Assess changes in the circulating regulatory B-cell population.
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California, Department of Neurology
state: California
Study officials:
affiliation: University of Southern California
name: Brett T Lund, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kashani N, Kelland EE, Vajdi B, Anderson LM, Gilmore W, Lund BT. Immune Regulatory Cell Bias Following Alemtuzumab Treatment in Relapsing-Remitting Multiple Sclerosis. Front Immunol. 2021 Oct 28;12:706278. doi: 10.3389/fimmu.2021.706278. eCollection 2021.