Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis (CAM-THY)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Cambridge University Hospitals NHS Foundation Trust
Sponsor:
Information provided by (Responsible Party):
Alasdair Coles, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01712945
First received: October 19, 2012
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to test a novel strategy to prevent the clinical problem of secondary autoimmunity following alemtuzumab treatment of multiple sclerosis.

The hypothesis is that autoimmunity after alemtuzumab can be prevented by giving a drug that promotes thymic T cell regeneration (Palifermin, Kepivance®).


Condition Intervention Phase
Multiple Sclerosis
Drug: Palifermin
Drug: Alemtuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • incidence of clinical autoimmunity [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: Yes ]
    The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab


Secondary Outcome Measures:
  • Absolute numbers of naive T cells [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: No ]
    Absolute numbers of naive T cells

  • Safety events [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: Yes ]
    Safety outcomes - incidence and nature of adverse events


Other Outcome Measures:
  • Time at which autoimmunity develops [ Time Frame: Within 30 months after alemtuzumab ] [ Designated as safety issue: No ]
  • Reconstitution of lymphocyte subsets [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: No ]
    Percentage of naive, central memory, effector memory and effector memory RA cells within the CD4 and CD8 T cell populations

  • T cell receptor (TCR) clonality [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: No ]
    T cell receptor (TCR) clonality

  • Thymic function [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: No ]
    Thymic function - determined by measuring TRECs

  • Thymic volume [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: No ]
    Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.

  • Thymic density [ Time Frame: within 30 months of starting treatment with alemtuzumab ] [ Designated as safety issue: No ]
    Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.


Estimated Enrollment: 86
Study Start Date: June 2012
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Palifermin (and Alemtuzumab)
Palifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
Drug: Palifermin
Palifermin (Kepivance®) administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose.
Other Names:
  • Kepivance
  • keratinocyte growth factor
Drug: Alemtuzumab
Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
Other Name: Campath-1H
Placebo Comparator: Placebo (and Alemtuzumab)
Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
Drug: Alemtuzumab
Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
Other Name: Campath-1H

Detailed Description:

This is a single-centre, double-blinded, randomised controlled trial of palifermin (Kepivance) vs. placebo in the prevention of autoimmunity following alemtuzumab treatment of multiple sclerosis.

The dose of palifermin (kepivance)used in this trial will be informed by a dose-escalation study.

  Eligibility

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

Inclusion Criteria:

  • Male or non-pregnant, non-lactating female patients
  • > 18 years of age, and <50 years of age inclusive
  • Diagnosis of MS using McDonald's 2010 criteria, including MRI abnormalities consistent with McDonald's 2010 criteria.
  • Onset of first MS symptoms within 10 years on the date the ICF is signed
  • EDSS score 0.0 to 5.0 (inclusive) at screening
  • At least 2 clinical episodes of MS in the 2 years prior to study entry, with at least 1 attack within 12 months, which may have occurred whilst on disease-modifying therapy, namely any beta interferon or glatiramer acetate.
  • Serum IL-7≤7pg/mL

Exclusion Criteria:

  • Any progressive form of multiple sclerosis
  • Previous thymectomy
  • Previous treatment with alemtuzumab, natalizumab, mitoxantrone, cyclophosphomide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids and disease-modifying therapies listed above)
  • History of malignancy
  • Personal history of clinically significant autoimmune disease, other than multiple sclerosis (including but not limited to: thyroid disease, immune cytopenias, inflammatory bowel disease, diabetes, lupus, severe asthma)
  • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
  • 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.
  • Seropositivity for human immunodeficiency virus (HIV)
  • Past or present hepatitis B infection (positive hepatitis B serology)
  • Pregnant women or male and female patients who do not agree to use effective contraception during the study.
  • Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
  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: NCT01712945

Contacts
Contact: Alasdair Coles, PhD FRCP 441223216751 ajc1020@medschl.cam.ac.uk
Contact: Joanne Jones, PhD MRCP 441223216751 jls53@medschl.cam.ac.uk

Locations
United Kingdom
Addenbrooke's Hospital Recruiting
Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
Contact: Karen May    441223216751    km480@medschl.cam.ac.uk   
Principal Investigator: Alasdair Coles, PhD FRCP         
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Alasdair Coles, Phd FRCP University of Cambridge
  More Information

Additional Information:
Publications:

Responsible Party: Alasdair Coles, Principal Investigator, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01712945     History of Changes
Other Study ID Numbers: EudraCT 2011-005606-30
Study First Received: October 19, 2012
Last Updated: October 23, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
Alemtuzumab
Palifermin
Reconstitution
Thymus

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Mitogens
Alemtuzumab
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014