Advanced MRI Measures of Repair in Alemtuzumab Treated Patients (iCAMMS-IST)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01307332
First received: January 26, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

There are two parts to this investigator sponsored trial (IST):

  1. To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
  2. To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.

Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Drug: MabCampath-1h
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Advanced Magnetic Resonance Imaging Measures of Repair in Alemtuzumab Treated Patients

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Changes in normal appearing white matter from baseline through month 24. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The MRI study is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination.


Secondary Outcome Measures:
  • To identify specific changes in T cell subsets and functions in Relapsing Remitting Multiple Sclerosis from baseline through month 48. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Analyzing changes is immune responsiveness may reveal critical information about the mechanisms by which alemtuzumab acts, confirm the importance of specific immune cell types or molecules as targets for alemtuzumab treatment or may also be useful for monitoring drug effectiveness and safety.


Estimated Enrollment: 25
Study Start Date: March 2011
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MabCampath-1h
Single arm, single cohort study, all subjects will be dosed with alemtuzumab.
Drug: MabCampath-1h
Drug:10 mg/mL alemtuzumab intravenous infusion. Form: Sterile, clear, colorless solution. Dosage: 2 cycles. Month 0 dosed over 5 consecutive days; month 12 dosed over 3 consecutive days.
Other Name: Alemtuzumab

Detailed Description:

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). There are many forms of MS; although the majority are Relapsing Remitting (RRMS) representing approximately 80% of the cases. The disease appears to be more inflammatory in RRMS as manifested by an increase in Gadolinium (Gd) enhancement on MRI and an increase in inflammatory bio-assay markers.

Alemtuzumab; a humanized monoclonal antibody that targets the CD52 molecule present on T and B lymphocytes, natural killer (NK) cells, and monocytes and macrophages; effects rapid and sustained lymphocyte depletion and is approved for the treatment of B-cell chronic lymphocytic leukemia in many countries under the names CAMPATH or MabCAMPATH.

There are two parts to this Investigator Sponsored Trial (IST):

  1. To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
  2. To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed, informed consent form
  • Age 18 to 50 years old (inclusive)
  • Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years of screening
  • Onset of MS symptoms within 15 years of screening
  • Neurostatus (EDSS) score 0.0 to 5.0 (inclusive)
  • 2 MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with 1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician.

Exclusion Criteria:

  • Received prior therapy for MS other than corticosteroids within 28 days of screening; e.g., interferon's, IV immunoglobulin, and glatiramer acetate
  • Exposure to natalizumab within 6 months of screening
  • Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other immunosuppressive agent other than systemic corticosteroid treatment
  • Has any progressive form of MS
  • History of malignancy (exception for basal cell skin carcinoma)
  • Previous hypersensitivity reaction to other immunoglobulin product
  • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
  • CD4+, CD8+, or CD19+ (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) count <LLN at Screening; if abnormal cell count(s) return to within normal limits, eligibility may be reassessed
  • Seropositivity for human immunodeficiency virus (HIV)
  • Significant autoimmune disease (e.g, immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel disease; severe psoriasis)
  • Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies
  • Active infection
  • Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis.
  • Infection with hepatitis B virus or hepatitis C virus
  • Of childbearing potential with a positive serum pregnancy test
  • Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period
  • Major psychiatric disorder that is not adequately controlled by treatment
  • Epileptic seizures that are not adequately controlled by treatment
  • Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results
  • Medical, psychiatric, cognitive, or other conditions
  • Confirmed platelet count the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at 100,000/L within the past year on a sample without clumping
  • Prior history of invasive fungal infections
  • Cervical high risk human papilloma virus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS).
  • Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only)
  • Any other illness or infection (latent or active) that, in the Investigator's opinion, could be exacerbated by alemtuzumab treatment
  • Any hepatic or renal function value grade 2 or higher at Screening, with the exception of hyperbilirubinemia due to Gilbert's syndrome.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307332

Locations
Canada, British Columbia
University of British Columbia Hospital
Vancouver, British Columbia, Canada, V6T 2B5
Sponsors and Collaborators
University of British Columbia
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Anthony Traboulsee, MD University of British Columbia
  More Information

Publications:
Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01307332     History of Changes
Other Study ID Numbers: H10-02482, 142402
Study First Received: January 26, 2011
Last Updated: December 10, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
Multiple Sclerosis
MS
Relapsing Remitting Multiple Sclerosis
RRMS
Alemtuzumab
Demyelination
Remyelination
Tolerogenic
T cells
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Alemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014