Alemtuzumab for ANCA Associated Refractory Vasculitis (ALEVIATE)

Study Description

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Brief Summary:

Overview:

This open label, randomized, multi-centre study will enroll and treat 24 patients with refractory AAV.

Aims:

To determine the clinical response and severe adverse event rates associated with alemtuzumab therapy among patients with relapsing or refractory ANCA associated vasculitis (AAV).

Hypothesis:

Treatment with alemtuzumab induces sustained remission in AAV and will reduce immunosuppressive and steroid exposure.

Condition or disease	Intervention/treatment	Phase
Vasculitis; Microscopic Polyangiitis; Granulomatosis With Polyangiitis; Wegener's	Drug: Alemtuzumab	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Alemtuzumab for ANCA Associated Refractory Vasculitis - a Study of Safety and Efficacy
Study Start Date :	February 2011
Estimated Primary Completion Date :	March 2014
Estimated Study Completion Date :	March 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Alemtuzumab - high dose (60mg); Alemtuzumab 30mg will be administered on Day 1 and Day 2 at 0 and 6 months	Drug: Alemtuzumab; Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months; Other Name: Campath 1H
Experimental: Alemtuzumab - low dose (30mg); Alemtuzumab 15mg will be administered on Day 1 and Day 2 at 0 and 6 months	Drug: Alemtuzumab; Alemtuzumab will be administered on Day 1 and Day 2 at 0 and 6 months; Other Name: Campath 1H

Outcome Measures

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Primary Outcome Measures :

1. Proportion of patients with a vasculitis response at 6 months [ Time Frame: 6 months ]
   Response includes patients in complete and partial remission. Complete remission (CR) is defined as a BVAS/WG of 0 for at least one month. Partial response (PR) is the absence of severe BVAS/WG items and at least 50% fall in BVAS/WG score from baseline.
2. Proportion of patients with a severe adverse event [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Proportion of patients with treatment failure [ Time Frame: 12 months ]
   Treatment failure is defined as the failure to achieve a vasculitis response by six months or a vasculitis relapse between 6 and 12 months
2. Combined damage assessment (CDA) scores [ Time Frame: 12 months ]
3. Non severe adverse events [ Time Frame: 12 months ]
4. Cumulative dose of corticosteroids [ Time Frame: 12 months ]
5. Time to remission [ Time Frame: 6 months ]
   Complete and partial
6. Relapse [ Time Frame: 12 months ]
7. Change in SF-36 [ Time Frame: 12 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. A diagnosis of AAV, according to a standardized definition
2. Active vasculitis with at least one severe or three non severe items of BVAS/WG activity (equivalent to BVAS/WG>3)
3. Previous therapy with either cyclophosphamide or methotrexate, in combination with prednisolone for at least 3 months.

Exclusion Criteria:

1. Age less than 18 or greater than 60 years
2. Creatinine > 150μmol/l (1.7mg/dl)
3. Total white count < 4x109/l or lymphocyte count < 0.5x109/l, or IgG < 5g/L, or neutrophil count < 1.5x109/l.
4. Severe lung haemorrhage with hypoxia (<85% on room air)
5. Severe gastrointestinal, central nervous system or cardiac vasculitis

6. Previous therapy with:

   1. Alemtuzumab at any time
   2. IVIg, infliximab, etanercept, adalimumab, abatacept, anti-thymocyte globulin or plasma exchange in past three months
   3. Rituximab within the past 6 months
7. Intensive care unit requirement
8. Active infection with HIV, hepatitis B or hepatitis C or other infection requiring parenteral or long-term oral antibiotics
9. History of ITP or platelet count at screening below 50,000 x 106/l
10. Pregnancy or inadequate contraception in pre-menopausal women
11. Breast feeding
12. Any condition judged by the investigator that would cause the study to be detrimental to the patient.
13. Any other multisystem autoimmune disease including Churg Strauss angiitis, systemic lupus erythematosus, anti-GBM disease and cryoglobulinaemia
14. Any previous or current history of malignancy (other than resected basal cell carcinoma)

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: David RW Jayne, MD FRCP	00441223586796	dj106@cam.ac.uk
Contact: Rona M Smith, MA MRCP	00441223217259	ronasmith@doctors.net.uk

Locations

United Kingdom
Addenbrooke's Hospital, University of Cambridge NHS Foundation Trust	Recruiting
Cambridge, United Kingdom, CB20QQ
Contact: David RW Jayne, MD FRCP 00441223586796 dj106@cam.ac.uk
Principal Investigator: David RW Jayne, MD FRCP

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

Investigators

Principal Investigator:	David RW Jayne, MD MRCP	Cambridge University Hospitals NHS Foundation Trust

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Dr David Jayne, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT01405807 History of Changes
Other Study ID Numbers:	AL1.1; 2009-017087-17 ( EudraCT Number )
First Posted:	July 29, 2011
Last Update Posted:	July 29, 2011
Last Verified:	July 2011

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:

Vasculitis; ANCA; Refractory

Additional relevant MeSH terms:

Vasculitis; Systemic Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis	Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Alemtuzumab; Antineoplastic Agents