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

April 17, 2018 updated by: University of Manitoba

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Transplant Manitoba Adult Kidney Transplant Program, Health Sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • de novo DSA occurring equal to or greater than15 years after kidney transplant
  • Screening biopsy with equal to or greater than cg2 on Banff criteria
  • Cumulative/lifetime dose of cyclophosphamide, including anticipated total study dose (calculated according to Creatinine Clearance and mg/kg/day) equal to or greater than 36 g.
  • Any condition that, in the opinion of the investigator, would pose risk to the subject's safe participation in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Procytox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microvascular inflammation
Time Frame: month 6
Histologic resolution of acute antibody-mediated inflammation in a 6 month post-treatment biopsy (Banff histology scores: g, v, ptc, C4d +ve)
month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
titre of donor specific antibody (DSA)
Time Frame: 6 and 12 months
Change in the level of de novo DSA between enrolment and at 6 and 12 months post-enrollment
6 and 12 months
antibody-mediated tissue injury
Time Frame: month 6
Change in antibody-mediated tissue injury between the enrollment and post-treatment kidney transplant biopsy samples
month 6
Urine Albumin/Creatinine ratios
Time Frame: month 6 and 12
Change in urine albumin/creatinine ratio between enrolment and 6 and 12 month post-enrolment samples
month 6 and 12
Creatinine Clearance and estimated GFR
Time Frame: month 6 and 12
Evaluation of Creatinine Clearance, and estimated GFR using the Chronic Kidney Disease Epidemiology (CKR-EPI) equation
month 6 and 12
Graft Survival
Time Frame: month 6 and 12
month 6 and 12
Patient Survival
Time Frame: month 6 and 12
month 6 and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Investigators

  • Principal Investigator: Peter W Nickerson, MD, University of Manitoba
  • Study Chair: David N Rush, MD, University of Manitoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2013

Primary Completion (Actual)

January 18, 2018

Study Completion (Actual)

January 18, 2018

Study Registration Dates

First Submitted

June 25, 2012

First Submitted That Met QC Criteria

June 27, 2012

First Posted (Estimate)

June 28, 2012

Study Record Updates

Last Update Posted (Actual)

April 19, 2018

Last Update Submitted That Met QC Criteria

April 17, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TMCT-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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