A Study of Palifermin for the Reduction of Oral Mucositis in Subjects With Multiple Myeloma

A Double-Blind, Randomized, Placebo-controlled Study of Two Different Schedules of Palifermin for Reduction in Severity of Oral Mucositis in Subjects With Multiple Myeloma Receiving Melphalan Followed by Autologous Blood Stem Cell Transplantation

The purpose of this study was to evaluate the efficacy and effect of palifermin on the incidence of oral mucositis in subjects with multiple myeloma receiving Melphalan followed by autologous peripheral blood stem cell transplantation. Amendment 01 (April 07) introduced three cataract assessments to be carried out at Screening, Month 6 and Month 12 in response to FDA and EMEA follow up measures.

This was a double-blind, placebo-controlled, randomized, multicenter Phase IIIb study of palifermin given before and after dose chemotherapy (total 6 doses) or before dose chemotherapy only (total 3 doses), in subjects with Multiple Myeloma (MM)receiving high dose melphalan (chemotherapy), in a 1-day schedule, followed by autologous Peripheral Blood Stem Cell Transplantation (PBSCT).

All subjects were to be followed for disease progression, second primary tumors, additional malignancies and survival for up to 10 years.

Planned: 275 subjects, in fact, 281 subjects were randomized. Randomized: 115 subjects to palifermin pre/post-CT, 109 subjects to palifermin pre-CT and 57 subjects to placebo Analyzed: 281 subjects in the full analysis set, 277 subjects in the safety subset.

Efficacy Oral cavity assessment, patient reported outcome (PRO) questionnaires (Oral Mucositis Daily Questionnaire [OMDQ], Functional Assessment of Cancer Therapy Esophageal [FACT-E], European Quality of Life Utility Scale [EQ 5D], Mucositis Chronic Symptoms Questionnaire [MCSQ]).

Safety Physical examination (including body temperature), concomitant medications, transfusions, vital signs, laboratory assessments (hematology, chemistry), cataract assessments, adverse events (AEs).

Inclusion Criteria:

• Multiple myeloma (MM) subjects scheduled to receive high-dose Melphalan in a one day schedule followed by autologous peripheral blood progenitor cell (PBSCT)
• Body Mass Index (BMI) ≤ 35
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, or an ECOG status of 3 if the reason for a status of 3 is exclusively due to MM (e.g. pathological fracture)
• Functional hematopoietic, hepato-renal and pulmonary systems
• Subjects at minimum with a baseline best corrected visual acuity (BCVA) of 20/40, (6/12 or 0.5 on the decimal scale) or better using the ETDRS chart in one eye
• Subject at minimum with one eye with a natural, intact lens
• Subject who has a LOCS III score at baseline of P < 1.0, C < 2.0 and NO < 2.0 in at least one eye
• Women in child bearing potential must have a negative pregnancy test

Exclusion Criteria:

• Presence or history of any other malignancy (other than curatively treated basal cell or squamous cell carcinoma of the skin, in situ cervical carcinoma, or other surgically cured malignancy, without evidence of disease for > 3 years
• Prior autologous or allogeneic transplants
• Prior treatment with palifermin, or other fibroblast or keratinocyte growth factors
• Receiving dialysis
• History of cataract surgery in both eyes
• Incapable of being responsive to mydriatic agents
• History of other ocular disease (e.g., macular degeneration, glaucoma, corneal disease) that would make assessment of visual status difficult
• Subject is scheduled to undergo cataract surgery
• Subject with any disease, that in the opinion of the ophthalmologist, could adversely effect the subject's vision during the course of the study
• Currently active oral mucositis infection
• Positive for HIV, hepatitis B or C
• Subject is unable or unwilling to follow with study procedures
• Subject is pregnant or is breast feeding
• Subject has not agreed to use adequate contraceptive precautions