search
Back to results

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

Primary Purpose

Multiple Sclerosis

Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Palifermin
Alemtuzumab
Sponsored by
Cambridge University Hospitals NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Multiple Sclerosis focused on measuring Alemtuzumab, Palifermin, Reconstitution, Thymus

Eligibility Criteria

18 Months - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Addenbrooke's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Palifermin (and Alemtuzumab)

Placebo (and Alemtuzumab)

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

incidence of clinical autoimmunity
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
Absolute numbers of naive T cells
Safety events
Safety outcomes - incidence and nature of adverse events

Full Information

First Posted
October 19, 2012
Last Updated
April 26, 2019
Sponsor
Cambridge University Hospitals NHS Foundation Trust
search

1. Study Identification

Unique Protocol Identification Number
NCT01712945
Brief Title
Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis
Acronym
CAM-THY
Official Title
Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab
Study Start Date
June 2012 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cambridge University Hospitals NHS Foundation Trust

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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®).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Alemtuzumab, Palifermin, Reconstitution, Thymus

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Palifermin (and Alemtuzumab)
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo (and Alemtuzumab)
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Palifermin
Other Intervention Name(s)
Kepivance, keratinocyte growth factor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Campath-1H
Intervention Description
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).
Primary Outcome Measure Information:
Title
incidence of clinical autoimmunity
Description
The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab
Time Frame
within 30 months of starting treatment with alemtuzumab
Secondary Outcome Measure Information:
Title
Absolute numbers of naive T cells
Description
Absolute numbers of naive T cells
Time Frame
within 30 months of starting treatment with alemtuzumab
Title
Safety events
Description
Safety outcomes - incidence and nature of adverse events
Time Frame
within 30 months of starting treatment with alemtuzumab
Other Pre-specified Outcome Measures:
Title
Time at which autoimmunity develops
Time Frame
Within 30 months after alemtuzumab
Title
Reconstitution of lymphocyte subsets
Description
Percentage of naive, central memory, effector memory and effector memory RA cells within the CD4 and CD8 T cell populations
Time Frame
within 30 months of starting treatment with alemtuzumab
Title
T cell receptor (TCR) clonality
Description
T cell receptor (TCR) clonality
Time Frame
within 30 months of starting treatment with alemtuzumab
Title
Thymic function
Description
Thymic function - determined by measuring TRECs
Time Frame
within 30 months of starting treatment with alemtuzumab
Title
Thymic volume
Description
Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.
Time Frame
within 30 months of starting treatment with alemtuzumab
Title
Thymic density
Description
Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.
Time Frame
within 30 months of starting treatment with alemtuzumab

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alasdair Coles, Phd FRCP
Organizational Affiliation
University of Cambridge
Official's Role
Principal Investigator
Facility Information:
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
21397567
Citation
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011 Apr;10(4):338-48. doi: 10.1016/S1474-4422(11)70020-5.
Results Reference
background
PubMed Identifier
19546505
Citation
Jones JL, Phuah CL, Cox AL, Thompson SA, Ban M, Shawcross J, Walton A, Sawcer SJ, Compston A, Coles AJ. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Invest. 2009 Jul;119(7):2052-61. doi: 10.1172/JCI37878. Epub 2009 Jun 22.
Results Reference
background
PubMed Identifier
16231285
Citation
Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005 Nov;35(11):3332-42. doi: 10.1002/eji.200535075.
Results Reference
background
PubMed Identifier
18946064
Citation
CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
Results Reference
background
PubMed Identifier
18025186
Citation
Bruinsma M, van Soest PL, Leenen PJ, Lambrecht BN, Cupedo T, Lowenberg B, Cornelissen JJ, Braakman E. Keratinocyte growth factor induces expansion of murine peripheral CD4+Foxp3+ regulatory T cells and increases their thymic output. J Immunol. 2007 Dec 1;179(11):7424-30. doi: 10.4049/jimmunol.179.11.7424.
Results Reference
background
PubMed Identifier
1560201
Citation
Miller RD, Caulfield MJ, Calkins CE. Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice. J Immunol. 1992 Apr 15;148(8):2452-5.
Results Reference
background
PubMed Identifier
17138819
Citation
Min D, Panoskaltsis-Mortari A, Kuro-O M, Hollander GA, Blazar BR, Weinberg KI. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007 Mar 15;109(6):2529-37. doi: 10.1182/blood-2006-08-043794. Epub 2006 Nov 30.
Results Reference
background
PubMed Identifier
31063156
Citation
Coles AJ, Azzopardi L, Kousin-Ezewu O, Mullay HK, Thompson SA, Jarvis L, Davies J, Howlett S, Rainbow D, Babar J, Sadler TJ, Brown JWL, Needham E, May K, Georgieva ZG, Handel AE, Maio S, Deadman M, Rota I, Hollander G, Dawson S, Jayne D, Seggewiss-Bernhardt R, Douek DC, Isaacs JD, Jones JL. Keratinocyte growth factor impairs human thymic recovery from lymphopenia. JCI Insight. 2019 May 7;5(12):e125377. doi: 10.1172/jci.insight.125377.
Results Reference
derived
Links:
URL
http://www.colescambridge.org.uk/trial%20participation.htm
Description
Information for patients on protocol

Learn more about this trial

Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis

We'll reach out to this number within 24 hrs