Study of Therapeutic Monitoring of Mycophenolate Mofetil (MMF/CellCept) After Kidney Transplantation

Roche

Status and phase: Completed; Phase 4

Conditions: Kidney Transplantation

Treatments: Drug: Tacrolimus; Drug: Cyclosporine; Drug: Mycophenolate mofetil

Study type: Interventional

Funder types: Industry

Identifiers

NCT00087581

ML17225

Details and patient eligibility

About

This three-arm study will evaluate the efficacy and safety of various dosing regimens of MMF combined with various dosing regimens of calcineurin inhibitor (CNI), either cyclosporine or tacrolimus, in participants who have undergone kidney transplantation. Participants will be randomized to one of three dosing regimens to receive concentration-controlled MMF with reduced CNI, concentration-controlled MMF with standard CNI, or fixed-dose MMF with standard CNI. Participants will be followed for 20-24 months after randomization.

Enrollment: 720 patients

Sex: All

Ages: 13 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or females 13-75 years of age
• Single organ recipient (kidney only) from living (related or unrelated) or cadaveric heart-beating donors
• Receiving first or second kidney transplant

Exclusion criteria

• Immunosuppressive therapy (except for 48 hours prior to transplantation and corticosteroid treatment) within previous 28 days for a first transplant and 3 months for a second transplant
• History of malignancy in last 5 years (except successfully treated localized non-melanoma skin cancer)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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720 participants in 3 patient groups

Group A: Monitored MMF + Reduced CNI

Experimental group

Description:

Group A will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or intravenous (IV) form. The initial dose will be at least 1 gram twice a day (BID) in adults and 600 milligrams per meter-squared (mg/m\^2) in pediatrics. Subsequent doses will be adjusted to maintain blood mycophenolic acid (MPA) levels greater than or equal to (≥) 1.3 micrograms per milliliter (μg/mL) with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain reduced blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 nanograms per milliliter (ng/mL); Days 30-90, 125-165 ng/mL; Days 90 through end of study, 95-145 ng/mL. Tacrolimus target concentrations areas follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL; Days 90 through end of study, 3-5 ng/mL.

Treatment:

Drug: Cyclosporine

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Group B: Monitored MMF + Full CNI

Experimental group

Description:

Group B will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. Subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.

Treatment:

Drug: Cyclosporine

Drug: Tacrolimus

Drug: Mycophenolate mofetil

Group C: Fixed MMF + Full CNI

Experimental group

Description:

Group C will receive fixed-dose MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. Subsequent doses are not to be adjusted, except in the case of unacceptable toxicity. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.

Treatment:

Drug: Cyclosporine

Drug: Tacrolimus

Drug: Mycophenolate mofetil