Repeat-Dose Pharmacokinetics and Pharmacodynamics of Bortezomib in Patients With Relapsed Multiple Myeloma
Repeat-Dose Pharmacokinetics and Pharmacodynamics of Bortezomib in Patients With Relapsed Multiple Myeloma
The purpose of this study is to characterize the clinical pharmacokinetic and pharmacodynamic
 profiles of the 2 doses of VELCADE (bortezomib) for Injection. Patients who volunteer to
 participate in the pharmacogenetic portion of the study, an additional blood sample will be
 collected before the Cycle 1 Day 1 dose of bortezomib to assess the genotype of drug
 metabolizing enzymes.
Male and female adult patients 18 years or older with a diagnosis of relapsed multiple
 myeloma requiring therapy will be eligible for this study.

 Key inclusion criteria include:

 Karnofsky Performance Status (KPS) equal to or greater then 70%, normal liver function
 tests (aspartate transaminase [AST] or alanine transaminase [ALT] equal to or less then 2 x
 upper limit of normal [ULN], total bilirubin equal to or less then 1.5 x ULN), hemoglobin
 equal to or greater then 10 g/dL, platelets equal to greater then 50 x 10 to ninth power/L,
 and absolute neutrophil count (ANC) equal to or greater then 1000/uL; calculated creatinine
 clearance equal to or greater then 50 mL/min, and normal serum calcium.

 Key exclusion criteria include:

 Patients with significant cardiac disease, equal to or greater then Grade 2 neuropathy,
 active hepatitis, HIV infection, secondary malignancy, POEMS syndrome, plasma cell
 leukemia, or who are transfusion-dependent or received extensive radiation therapy,
 systemic chemotherapy, or other antineoplastic therapy within 4 weeks of enrollment will be
 excluded. Patients taking concurrent medications at entry that may act as inducers or
 inhibitors of CYP 3A4 are excluded. Patients receiving thalidomide must discontinue that
 drug at least 2 weeks prior to enrollment. Patients receiving concurrent corticosteroids
 must have tapered their dose of corticosteroid to to equal to or less then 10 mg/day of
 prednisone or prednisone equivalent at least 2 weeks prior to enrollment.