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
Overview
- Phase
- Phase 3
- Intervention
- Palifermin before only
- Conditions
- Multiple Myeloma
- Sponsor
- Swedish Orphan Biovitrum
- Enrollment
- 281
- Locations
- 1
- Primary Endpoint
- Maximum Severity of Oral Mucositis (World Health Organization (WHO) Grades 0/1, 2, 3, or 4)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Eligibility Criteria
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
Arms & Interventions
Palifermin before only
Subjects received palifermin before-high dose chemotherapy (total 3 doses) and matched placebo after-high dose chemotherapy (total 3 doses)
Intervention: Palifermin before only
Placebo (suger pill)
Subjects received matched placebo before- and after-high dose chemotherapy
Intervention: Placebo
Palifermin before and after
Subjects received palifermin before- and after-high dose chemotherapy (total of 6 doses)
Intervention: Palifermin before and after
Outcomes
Primary Outcomes
Maximum Severity of Oral Mucositis (World Health Organization (WHO) Grades 0/1, 2, 3, or 4)
Time Frame: at Day 32
For the primary efficacy endpoint maximum severity of Oral Mucositis (OM) was assessed, the number of participants who had the different severity. To assess severity of OM, a 5-grade WHO scale (0, 1, 2, 3, or 4) was used. 0 = no findings or erythema only, 1= soreness present with or without erythema, 2=ulcers present but able to take solid food, 3 =ulcers present and only able to take liquids, 4 =ulcers present/not able to take anything orally.
Incidence of Cataract Development or Progression at Month 12.
Time Frame: 12 months
Number of participants from the primary cataract subset showing an increase from baseline of \>= 0.3 in the Lens Opacities Classification System III (LOCS III score). The LOCS III is a standard system used for grading and comparison of cataract severity and type. The ophthalmologist trained in LOCS III uses a slit lamp for examining the lens of the eye. The classification evaluates four features: posterior subcapsular cataract(P),cortical cataract(C),nuclear opalescence(NO) and nuclear color(NC). NO and NC are graded on a decimal scale of 0.1 to 6.9, based on a set of 6 standardized photographs. C and P are graded on a decimal scale of 0.1 to 5.9, based on a set of 5 standardized photographs each. In the current study, cataract development or progression was defined as an increase from baseline of ≥ 0.3 on any of the three features P, C or NO (NC is of less importance and has not been analysed further in this study).
Secondary Outcomes
- Time Death or Disease Progression(During long-term follow up phase (maximum of 10 years))
- Duration of Ulcerative Mucositis (WHO Grades 2, 3, and 4)(at Day 32)
- Incidence of Cataract Development or Progression (Change of ≥0.3 in Lens Opacities Classification System III (LOCS III Score)) at Month 6.(6 Months)
- Incidence of a Decreased From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by a Change of 10 Letters on the ETDRS (Early Termination Diabetic Retinopathy Study) at 4 Meters at Months 12.(Month 12)
- Incidence of Adverse Events and Laboratory Abnormalities(at Day 32)
- Incidence Ulcerative Mucositis (WHO Grades 2, 3, and 4)(at Day 32)
- The Area Under the Curve (AUC) Was Calculated From the Patient-reported Outcome Mouth and Throat Soreness (MTS) Score.(at Day 32)
- Incidence of a Decreased From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by a Change of 10 Letters on the ETDRS (Early Termination Diabetic Retinopathy Study) at 4 Meters at Months 6(Months 6)
- Overall Survival(During long-term follow up phase (maximum of 10 years))
- Incidence of Second Primary Malignancies or Other Malignancies(During long-term follow up phase (maximum of 10 years))
- Incidence of an Increase Posterior Subcapsular Cataract (P), Cortical Cataract (C) and Nuclear Opalescence (NO) at Month 6 and 12(at Month 6 and Month 12)
- Change From Baseline in Posterior Subcapsular (P), Cortical (C) Cataract and Nuclear Opalescence (NO) on the Lens Opacities Classification System III (LOCS III) Scale at Months 6.(Months 6)
- Change From Baseline in Posterior Subcapsular (P), Cortical (C) Cataract and Nuclear Opalescence (NO) on the Lens Opacities Classification System III (LOCS III) Scale at Months 12.(Months 12)
- Progression Free Survival(During long-term follow up phase (maximum of 10 years))