Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients

Optimizing Immunosuppression in Low-Risk Older Adult Kidney Transplant Recipients (OPTIMA-KT): A Prospective, Randomized, Open-Label, Blinded-Endpoint Single-Site Pilot/Feasibility Trial of Biomarker-Guided Mycophenolate Mofetil Elimination

Most kidney transplant recipients take a combination of anti-rejection medicines for the rest of their life. One of these is called mycophenolate mofetil (MMF), also known by the brand name CellCept. While MMF helps protect the kidney, taking it for many years can cause infections, low blood counts, stomach problems, and a higher risk of certain cancers, problems that older adults are especially likely to experience.

We are doing this study to learn whether carefully and slowly stopping MMF in older adults who are doing well after their transplant is as safe as continuing MMF, when we use blood and urine tests to closely watch for any early signs of trouble. The information learned could help future kidney transplant patients use less medicine without losing their transplant.

To evaluate the feasibility, safety, protocol adherence, biomarker monitoring completion, and preliminary clinical event rates associated with stepwise MMF elimination over 6 months compared with standard-of-care immunosuppression in low-risk older adult kidney transplant recipients.

Secondary objectives. To compare between arms: eGFR trajectory and proteinuria at Months 6 and 12; infection incidence (including CMV and BK), hospitalization, and adverse drug events; de novo DSA incidence and time to de novo DSA; and the kinetics and predictive performance of dd-cfDNA and urine CXCL9 and CXCL10 for rejection and de novo DSA.

Exploratory objectives. To assess the association between PIRCHE-II score and individual primary endpoint components; the performance of combined biomarker panels versus single biomarkers; health-related quality of life and patient-reported outcomes through Month 12; and cost and healthcare resource utilization through Month 12 across study arms.

Inclusion Criteria:

• Greater than 60 years of age
• Greater than 12 months from kidney transplant
• Stable maintenance tacrolimus- based immunosuppression for at least 3 months without dose changes greater than 25%
• PIRCHE-II score less than or equal to 65 calculated from available donor and recipient HLA typing
• Ability to provide written informed consent and comply with study procedures

Exclusion Criteria:

• Multi-organ transplant or prior graft loss due to rejection
• Maintenance immunosuppression including belatacept, cyclosporine, azathioprine, sirolimus, or other agents in lieu of tacrolimus or MMF
• Steroid-free regimen
• Active malignancy (excluding non-melanoma skin cancer)
• Uncontrolled infection
• BK viremia greater than 10,000 copies/mL, or BK nephropathy
• High immunologic risk (any preformed DSA, positive crossmatch, or biopsy-proven rejection within the prior 6 months)
• Pregnancy, breastfeeding, self-reported pregnancy, positive pregnancy test during screening if testing is indicated, or inability/unwillingness to comply with required pregnancy prevention measures if of childbearing potential
• Inability to comply with study procedures including monthly visits and biospecimen collection
• Concurrent participation in another conflicting interventional trial.