To assess and compare the pharmacokinetics of Melphalan HCL for Injection (Propylene Glycol-Free) versus Alkeran for Injection in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT).
This study will be a multicenter, open-label, randomized, comparative, cross-over study of high-dose Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection conducted in 24 patients who have symptomatic MM and qualify for ASCT. During the Study Period, patients will be randomized to receive 100mg/m2 of either Melphalan HCl for Injection (Propylene Glycol-Free) or Alkeran for Injection on Day -3 and the alternate drug product on Day -2. Blood samples for pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula each day of melphalan dosing (Day -3 and Day -2). Following one day of rest after the myeloablative conditioning (Day -1), patients will receive an autologous graft.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Patients will be randomized to receive 100 mg/m2 of Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and Alkeran for Injection on Day -2 prior to ASCT.
Patients will be randomized to receive 100 mg/m2 of Alkeran for Injection on Day -3 and Melphalan HCL for Injection (Propylene Glycol-Free)on Day -2 prior to ASCT.
University of Kansas Medical Center/University of Kansas Cancer Center and Medical Pavillion
Kansas City, Kansas, United States
Area Under the Curve (0-t)
AUC (0-t) was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations. The AUC results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
Time frame: Day -3 and Day -2
Concentration-Max (Cmax)
Cmax was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations. The Cmax results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
Time frame: Day -3 and Day -2
Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
ANC \<0.5 × 109/L, absolute lymphocyte count (ALC) \<0.1 × 109/L, platelet count \<20,000/mm3, or bleeding requiring transfusion. The first of 2 consecutive days for which cell counts drop below these cutoff levels was recorded as the date of myeloablation. Since the two treatments were administered consecutively with 1 day rest, the time to myeloablation and myeloablation rate was measured after both treatments were administered. Comparison of sequence effect was not planned in the study and due to small sample size, it was not performed.
Time frame: 30 days
Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Neutrophil engraftment was defined as the first day of 3 consecutive days where ANC (absolute neutrophil count) was higher than 500/ul. The two drug treatments in this cross-over design were administered on 2 subsequent days (Day -3 and Day -2). No per arm analysis was performed. Since the two treatments were administered consecutively with 1 day rest, the time to engraftment and engraftment rate was measured after both treatments were administered.
Time frame: 30 days