Evaluation of Single-Dose Palifermin To Reduce Oral Mucositis (OM) in Fractionated Total Body Irradiation (fTBI) and High Dose (HD) Chemotherapy with Autologous Peripheral Blood Progenitor Cell (PBPC) Transplantation.

For some patients (pts) with hematologic malignancies (HM) undergoing PBPC transplantation, the approved regimen of 3 daily doses of palifermin 60 μg/kg prior to myeloablative conditioning therapy may be inconvenient. This study was initially developed to demonstrate the non-inferiority of various collapsed pre-conditioning dosing regimens (180 μg/kg) in reducing the incidence of severe OM (WHO grade 3 or 4) induced by fTBI and HD chemotherapy in pts with HM undergoing PBPC transplantation. The study was stopped early because of slower than expected accrual.

Methods: Pts were 18 to 74 years old with HM, a Karnofsky performance score ≥70%, and eligible for fTBI (12 Gy) followed by optional VP-16 (60 mg/kg) and cyclophosphamide (100 mg/kg), and autologous PBPC support. Pts were randomized (1:1:1:1) to receive palifermin 60 μg/kg administered once daily for 3 days prior to the start of fTBI (Arm A) versus palifermin 180 μg/kg administered once only on day -1 (Arm B); day -2 (Arm C); or day -3 (Arm D) prior to the start of fTBI and stratified by VP-16 use and by the number of days of TBI fractions. All pts received palifermin 60 μg/kg for 3 days post transplant (days 0, 1, 2). Results are summarized as point estimates. Efficacy was analyzed for all evaluable patients as randomized; sensitivity analyses were done for all evaluable patients as treated.

Results: Of the 47 pts randomized, 1 pt was excluded from analyses due to delayed informed consent. The primary efficacy endpoint, incidence of severe OM, is summarized in Table 1. The overall incidence of severe OM for all pts was 61% (28/46), with a mean duration (SD) of 4.3 days (4.4). Severe OM incidences were 82% (9/11) in Arm A and 54% (19/35) in the combined collapsed dose groups (Arms B+C+D). Severe OM rates were 60% (6/10), 31% (4/13), and 75% (9/12) in Arms B, C and D, respectively. A similar distribution of the incidence of severe OM was seen in the sensitivity analysis (Table 1). All arms had a similar incidence of adverse events.

Conclusion: The overall incidence and duration of severe OM observed in this trial was consistent with the efficacy data of palifermin demonstrated in the pivotal randomized phase 3 trial (Spielberger et al, NEJM 351:10–17, 2004). The collapsed dosing regimen (180 μg/kg) was well tolerated, and the efficacy of palifermin in the collapsed dose arms is similar to Arm A, possibly allowing for increased patient and caregiver convenience. The small sample sizes limit the ability to compare the individual collapsed dose arms; however, the timing of palifermin collapsed dose administration may have an impact on the efficacy of OM reduction.