Pharmacokinetics-based Mycophenolate Mofetil Dosing for GVHD Prevention

• Status: Completed
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Bone marrow transplantation (BMT) is used to successfully treat high-risk forms of leukemia, lymphoma, and other childhood cancers that were once considered incurable. A major barrier to the application of this life-saving treatment is acute graft-versus-host disease (GVHD) which develops in approximately 30-80% of patients and is a leading cause of death from transplant complications. Current GVHD prevention methods are not very efficacious and lead to unacceptable side effects. Mycophenolate mofetil (MMF), an anti-rejection medication used in solid organ transplants, has shown great promise in BMT recipients. The effectiveness of MMF depends on blood levels of mycophenolic acid (MPA, the active form of MMF). Different patients have been found to have different blood levels of MPA when they are given the same dose of MMF. The purpose of this study is to study a novel method of giving MMF based on its metabolism (pharmacokinetics) to achieve desired blood levels of MPA for prevention of GVHD. Non-invasive ways of monitoring the drug exposure will also be studied. The ultimate goal of this study is to improve approaches to GVHD prevention and improve outcomes of BMT in children.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pittsburgh
• Treatments: Mycophenolate mofetil; Mycophenolic Acid

Criteria

Inclusion Criteria:

• Patients must be between 6 months and 21 years of age.

• Recipients of an allogeneic blood and marrow transplant (BMT).

• Stem cell sources should be bone marrow or umbilical cord blood.

• Bone marrow or cord blood unit: Sibling should be HLA matched at A, B and DRB1 loci. Unrelated cord blood unit should be at a minimum 4/6 matched at allele level on HLA A, B and DRB1 loci. Unrelated donor should be HLA allele level matched at A, B, C and DRB1 loci.

• Minimum prefreezing nucleated cell dose for cord blood units: 3x10^7/kg for malignant diseases and 5x10^7/kg for nonmalignant diseases.

• Conditioning regimen must be myeloablative in intensity. Examples include but are not limited to Cy/TBI, BuCy 200, etc.

• Patients ≥ 16 years old must have a Karnofsky score ≥ 70%, and patients < 16 years old must have a Lansky score ≥ 70%.

• Renal: Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2.

• Hepatic: Total bilirubin ≤ 2.5 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase < 5 x upper limit of normal (ULN) for age.

• Cardiac: Left ventricular ejection fraction at rest > 40%, or shortening fraction > 26%, by echocardiogram or radionuclide scan.

• Pulmonary: FEV1, FVC, and DLCO (diffusion capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92% of room air.

Exclusion Criteria:

• Patients with a known hypersensitivity to MMF.

• Prior autologous or allogeneic BMT < 12 months prior to enrollment.

• Mismatched related donor.

• Mismatched unrelated marrow donor.

• Peripheral blood stem cell source.

• Reduced intensity conditioning.

• Uncontrolled bacterial, viral, fungal or other infection.

• Evidence of HIV infection or HIV positive serology.

• Requirement of supplemental oxygen.

• Patients who are pregnant (B-hCG positive) or breastfeeding. All females of 11 years of age or older and/or who have begun menstruating will be screened for hCG by either urinalysis or a blood sample in order to screen for pregnancy status, as per institutional BMT policy.