After March 2015, unable to enroll due to patients meeting exclusion criteria.

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.

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