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

• ClinicalTrials.gov Identifier: NCT03647722
• Recruitment Status: Terminated
• First Posted: August 27, 2018
• Last Update Posted: December 17, 2020
• Sponsor: University of Southern California
• Information provided by (Responsible Party): Brett T. Lund, University of Southern California

Study Description

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.

Condition or disease	Intervention/treatment
Multiple Sclerosis	Other: Assessment of leukocyte function.

Study Design

• Study Type: Observational
• Actual Enrollment: 97 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Assessing the Induction of Long-term Immune Regulation Following Treatment With Lemtrada® (Alemtuzumab).
• Actual Study Start Date: November 2, 2018
• Actual Primary Completion Date: November 1, 2020
• Actual Study Completion Date: November 30, 2020

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Assess changes in the circulating regulatory B-cell population. [ Time Frame: 12 months ]

Biospecimen Retention:   Samples Without DNA

Plasma and serum.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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.

Contacts and Locations

Locations

United States, California

University of Southern California, Department of Neurology

Los Angeles, California, United States, 90033

Sponsors and Collaborators

University of Southern California

Investigators

• Principal Investigator: Brett T Lund, Ph.D.; University of Southern California

More Information

• Responsible Party: Brett T. Lund, Assistant Professor, Neurology, University of Southern California
• ClinicalTrials.gov Identifier: NCT03647722
• Other Study ID Numbers: LemRegUSC
• First Posted: August 27, 2018
• Last Update Posted: December 17, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases