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

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Assessment of leukocyte function.

• Study Type: Observational
• Enrollment (Actual): 97

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California, Department of Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Southern California

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 2, 2018
• Primary Completion (ACTUAL): November 1, 2020
• Study Completion (ACTUAL): November 30, 2020

Study Registration Dates

• First Submitted: August 21, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (ACTUAL): August 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis
• Other Study ID Numbers: LemRegUSC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No