Alemtuzumab for ANCA Associated Refractory Vasculitis (ALEVIATE)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by Cambridge University Hospitals NHS Foundation Trust.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01405807
First received: July 27, 2011
Last updated: July 28, 2011
Last verified: July 2011
  Purpose

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 Intervention Phase
Vasculitis
Microscopic Polyangiitis
Granulomatosis With Polyangiitis
Wegener's
Drug: Alemtuzumab
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Alemtuzumab for ANCA Associated Refractory Vasculitis - a Study of Safety and Efficacy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Proportion of patients with a vasculitis response at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Proportion of patients with a severe adverse event [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of patients with treatment failure [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Treatment failure is defined as the failure to achieve a vasculitis response by six months or a vasculitis relapse between 6 and 12 months

  • Combined damage assessment (CDA) scores [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Non severe adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Cumulative dose of corticosteroids [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Time to remission [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Complete and partial

  • Relapse [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in SF-36 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: February 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
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: NCT01405807

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

No publications provided

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
Study First Received: July 27, 2011
Last Updated: July 28, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
Vasculitis
ANCA
Refractory

Additional relevant MeSH terms:
Wegener Granulomatosis
Vasculitis
Systemic Vasculitis
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
Alemtuzumab
Campath 1G
Antibodies, Neoplasm
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014