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

NCT ID: NCT03647722

Last Updated: 2020-12-17

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 97 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-11-02
• Study Completion Date: 2020-11-30

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.

Conditions

Multiple Sclerosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Lemtrada treated - 6 month

Patients that received their first course of treatment with Lemtrada approximately 6 months prior.

Assessment of leukocyte function.

Intervention Type: OTHER

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.

Assessment of leukocyte function.

Intervention Type: OTHER

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.

Assessment of leukocyte function.

Intervention Type: OTHER

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.

Assessment of leukocyte function.

Intervention Type: OTHER

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.

Assessment of leukocyte function.

Intervention Type: OTHER

The function and phenotype of regulatory B-cells, regulatory T-cells and alternatively-activated monocytes will be assessed directly ex vivo from PBMC.

Interventions

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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Brett T. Lund

Assistant Professor, Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brett T Lund, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

University of Southern California, Department of Neurology

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34777337 (View on PubMed)

Other Identifiers

LemRegUSC

Identifier Type: -

Identifier Source: org_study_id