Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis (CAM-THY)
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| ClinicalTrials.gov Identifier: NCT01712945 |
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Recruitment Status :
Terminated
(interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab)
First Posted : October 24, 2012
Last Update Posted : April 30, 2019
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Sponsor:
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Alasdair Coles, Cambridge University Hospitals NHS Foundation Trust
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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®).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis | Drug: Palifermin Drug: Alemtuzumab | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 40 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, 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 |
| Actual Study Start Date : | June 2012 |
| Actual Primary Completion Date : | August 2017 |
| Actual Study Completion Date : | October 2017 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Multiple sclerosis
| Arm | Intervention/treatment |
|---|---|
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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).
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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:
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 |
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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).
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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 |
Primary Outcome Measures :
- incidence of clinical autoimmunity [ Time Frame: within 30 months of starting treatment with alemtuzumab ]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 ]Absolute numbers of naive T cells
- Safety events [ Time Frame: within 30 months of starting treatment with alemtuzumab ]Safety outcomes - incidence and nature of adverse events
Other Outcome Measures:
- Time at which autoimmunity develops [ Time Frame: Within 30 months after alemtuzumab ]
- Reconstitution of lymphocyte subsets [ Time Frame: within 30 months of starting treatment with alemtuzumab ]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 ]T cell receptor (TCR) clonality
- Thymic function [ Time Frame: within 30 months of starting treatment with alemtuzumab ]Thymic function - determined by measuring TRECs
- Thymic volume [ Time Frame: within 30 months of starting treatment with alemtuzumab ]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 ]Thymic volume and density - as assessed by non-contrast enhanced, low dose CT scans of the chest performed at baseline and month 6.
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| Ages Eligible for Study: | 18 Months to 50 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01712945
Locations
| United Kingdom | |
| Addenbrooke's Hospital | |
| Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ | |
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Investigators
| Principal Investigator: | Alasdair Coles, Phd FRCP | University of Cambridge |
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
| First Posted: | October 24, 2012 Key Record Dates |
| Last Update Posted: | April 30, 2019 |
| Last Verified: | April 2019 |
Keywords provided by Alasdair Coles, Cambridge University Hospitals NHS Foundation Trust:
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Alemtuzumab Palifermin Reconstitution Thymus |
Additional relevant MeSH terms:
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Multiple Sclerosis Autoimmune Diseases Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases |
Immune System Diseases Alemtuzumab Mitogens Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents |