Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Cyclophosphamide Therapy for Refractory Antibody-Mediated Rejection (AMR) in Kidney Transplants

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Manitoba
Sponsor:
Information provided by (Responsible Party):
University of Manitoba
ClinicalTrials.gov Identifier:
NCT01630538
First received: June 25, 2012
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

The study hypothesis is that short-term low dose cyclophosphamide therapy will be effective in resolving inflammation in patients with late phase antibody-mediated rejection refractory to current standard of care treatment.


Condition Intervention Phase
Antibody Mediated Rejection
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Pilot Study of Cyclophosphamide Therapy for Refractory Antibody-Mediated Rejection in Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by University of Manitoba:

Primary Outcome Measures:
  • Microvascular inflammation [ Time Frame: month 6 ] [ Designated as safety issue: No ]
    Histologic resolution of acute antibody-mediated inflammation in a 6 month post-treatment biopsy (Banff histology scores: g, v, ptc, C4d +ve)


Secondary Outcome Measures:
  • titre of donor specific antibody (DSA) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    Change in the level of de novo DSA between enrolment and at 6 and 12 months post-enrollment

  • antibody-mediated tissue injury [ Time Frame: month 6 ] [ Designated as safety issue: No ]
    Change in antibody-mediated tissue injury between the enrollment and post-treatment kidney transplant biopsy samples

  • Urine Albumin/Creatinine ratios [ Time Frame: month 6 and 12 ] [ Designated as safety issue: No ]
    Change in urine albumin/creatinine ratio between enrolment and 6 and 12 month post-enrolment samples

  • Creatinine Clearance and estimated GFR [ Time Frame: month 6 and 12 ] [ Designated as safety issue: No ]
    Evaluation of Creatinine Clearance, and estimated GFR using the Chronic Kidney Disease Epidemiology (CKR-EPI) equation

  • Graft Survival [ Time Frame: month 6 and 12 ] [ Designated as safety issue: No ]
  • Patient Survival [ Time Frame: month 6 and 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: June 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cyclophosphamide
Cyclophosphamide 1.5 mg/kg orally daily for 180 days (26 weeks) adjusted for renal function.
Drug: Cyclophosphamide
Cyclophosphamide 1.5 mg/kg orally daily for 180 days adjusted for renal function
Other Name: Procytox

Detailed Description:

There is no consensus on the optimal treatment of de novo donor specific antibody-mediated rejection. Optimizing baseline immunosuppression (calcineurin inhibitor (CNI), anti-proliferative agent, and anti-inflammatory) is considered foundational but is insufficient. Pulse steroids are routinely used. A number of immunosuppressive approaches have been tried in uncontrolled trials. The strongest evidence, at least for early antibody-mediated rejection (< 6 months from transplant), exists for plasmapheresis, with or without low dose IVIg, or high dose IVIg alone. However, as noted in a recent FDA workshop, "while the literature suggests that [these agents] have evidence of efficacy for the management of acute antibody-mediated rejection, and could be considered as standard of care, treatment regimes have not been standardized or optimized." Moreover the evidence supporting efficacy of this approach in late, as opposed to early antibody-mediated rejection is distinctly lacking.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a living or deceased donor kidney transplant
  • Failed current standard of care for late antibody-mediated rejection
  • Persistent de novo donor specific antibody and a concurrent biopsy with histologic evidence of acute antibody-mediated inflammation
  • Adults with reproductive potential must agree to use approved methods of birth control while in the study

Exclusion Criteria:

  • Leukopenia (WBC) < 3.0 x 109/L
  • Creatinine Clearance less than or equal to 25 ml/min/1.73m2
  • HCV or HBV positive
  • BKV or CMV viremia assessed by PCR
  • Any active infection
  • Use of other investigational drugs within 4 weeks of study
  • Pregnancy/breast feeding/unwilling or unable to take birth control
  • Active malignancy
  • Any condition that, in the opinion of the investigator, would pose risk to the subject's safe participation in 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: NCT01630538

Contacts
Contact: Peter W Nickerson, MD 204-789-3375 peter.nickerson@med.umanitoba.ca
Contact: David N Rush, MD 204-787-7807 drush@hsc.mb.ca

Locations
Canada, Manitoba
Transplant Manitoba Adult Kidney Transplant Program, Health Sciences Centre Recruiting
Winnipeg, Manitoba, Canada
Contact: Peter W Nickerson, MD    204-789-3375    peter.nickerson@med.umanitoba.ca   
Contact: David N Rush, MD    204-787-7807    drush@hsc.mb.ca   
Principal Investigator: David N Rush, MD         
Sponsors and Collaborators
University of Manitoba
Investigators
Principal Investigator: Peter W Nickerson, MD University of Manitoba
Study Chair: David N Rush, MD University of Manitoba
  More Information

Publications:
Responsible Party: University of Manitoba
ClinicalTrials.gov Identifier: NCT01630538     History of Changes
Other Study ID Numbers: TMCT-01
Study First Received: June 25, 2012
Last Updated: August 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of Manitoba:
Transplantation

Additional relevant MeSH terms:
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014