Phase I dose-escalation trial of high-dose melphalan (M) with palifermin (P) for cytoprotection followed by autologous stem cell transplantation (ASCT) for myeloma (MM) patients with normal renal function (NRF).

6543 Background: Melphalan (M) exhibits a steep, log-linear dose effect with a potential for dose escalation to overcome M resistance. Severe oral mucositis (OM) at M ≥ 200 mg/m2 precludes dose escalation due to significant morbidity. P as a cytoprotective agent has demonstrated efficacy in reducing intensity and duration of OM in pts receiving intensive chemo-radiotherapy. We designed this study to determine the MTD of M in pts with NRF when used with P. Methods: We enrolled 19 pts from 07/2007 to 09/2009. We report data on 18 evaluable pts as 1 pt was removed. Pts were 18-74 years old,stage 2/3, ECOG PS ≤ 2, no active OM & eligible for ASCT. Dose-escalation proceeded (three-pt cohorts), at 20 mg/m2 increments, depending on the dose limiting toxicities (DLT). Level (L) 1 began at M 200 mg/m2 with P 60 mcg/kg/d, given as I.V. bolus on Day -5,-4, -3 and Day +1, +2 and +3 (PBSCs infused on Day 0). M was given on D-2 up to and including 280 mg/m2 (n = 6). If no symptomatic grade ≥ 3 DLTs were noted by day +3...