NCT01630538

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2013

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 25, 2012

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 28, 2012

Completed
11 months until next milestone

Study Start

First participant enrolled

June 1, 2013

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 18, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 18, 2018

Completed
Last Updated

April 19, 2018

Status Verified

April 1, 2018

Enrollment Period

4.6 years

First QC Date

June 25, 2012

Last Update Submit

April 17, 2018

Conditions

Antibody Mediated Rejection

Keywords

Transplantation

Outcome Measures

Primary Outcomes (1)

  • Microvascular inflammation

    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 Outcomes (6)

  • titre of donor specific antibody (DSA)

    6 and 12 months

  • antibody-mediated tissue injury

    month 6

  • Urine Albumin/Creatinine ratios

    month 6 and 12

  • Creatinine Clearance and estimated GFR

    month 6 and 12

  • Graft Survival

    month 6 and 12

  • +1 more secondary outcomes

Study Arms (1)

Cyclophosphamide

EXPERIMENTAL

Cyclophosphamide 1.5 mg/kg orally daily for 180 days (26 weeks) adjusted for renal function.

Drug: Cyclophosphamide

Interventions

CyclophosphamideDRUG

Cyclophosphamide 1.5 mg/kg orally daily for 180 days adjusted for renal function

Also known as: Procytox
Cyclophosphamide

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Transplant Manitoba Adult Kidney Transplant Program, Health Sciences Centre

Winnipeg, Manitoba, Canada

Location

Related Publications (2)

  • Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5):1157-67. doi: 10.1111/j.1600-6143.2012.04013.x. Epub 2012 Mar 19.

    PMID: 22429309BACKGROUND

  • Archdeacon P, Chan M, Neuland C, Velidedeoglu E, Meyer J, Tracy L, Cavaille-Coll M, Bala S, Hernandez A, Albrecht R. Summary of FDA antibody-mediated rejection workshop. Am J Transplant. 2011 May;11(5):896-906. doi: 10.1111/j.1600-6143.2011.03525.x.

    PMID: 21521465BACKGROUND

MeSH Terms

Interventions

Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Peter W Nickerson, MD

    University of Manitoba

    PRINCIPAL INVESTIGATOR

  • David N Rush, MD

    University of Manitoba

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 25, 2012

First Posted

June 28, 2012

Study Start

June 1, 2013

Primary Completion

January 18, 2018

Study Completion

January 18, 2018

Last Updated

April 19, 2018

Record last verified: 2018-04

Locations

CA(1)