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

June 25, 2012
August 7, 2014
June 2013
April 2015   (final data collection date for primary outcome measure)
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)
Same as current
Complete list of historical versions of study NCT01630538 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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
  • estimated GFR [ Time Frame: month 6 and 12 ] [ Designated as safety issue: No ]
    Evaluation of 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 ]
Not Provided
Not Provided
 
Cyclophosphamide Therapy for Refractory Antibody-Mediated Rejection (AMR) in Kidney Transplants
Phase II Pilot Study of Cyclophosphamide Therapy for Refractory Antibody-Mediated Rejection in Kidney Transplantation

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Antibody Mediated Rejection
Drug: Cyclophosphamide
Cyclophosphamide 1.5 mg/kg orally daily for 180 days adjusted for renal function
Other Name: Procytox
Experimental: Cyclophosphamide
Cyclophosphamide 1.5 mg/kg orally daily for 180 days (26 weeks) adjusted for renal function.
Intervention: Drug: Cyclophosphamide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
April 2016
April 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
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
Canada
 
NCT01630538
TMCT-01
Yes
University of Manitoba
University of Manitoba
Not Provided
Principal Investigator: Peter W Nickerson, MD University of Manitoba
Study Chair: David N Rush, MD University of Manitoba
University of Manitoba
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP