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

University of Manitoba

Status and phase

Terminated

Phase 2

Conditions

Antibody Mediated Rejection

Treatments

Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other

Identifiers

NCT01630538

TMCT-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

4 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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