Clinical trial NCT00434161: A Study of Palifermin for the Reduction of Oral Mucositis in Subjects With Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Palifermin
KGF
Clinical Trial
Oncology
Oral Mucositis
Multiple Myeloma
Cataract
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2007-02-12
Enrollment: 281
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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).

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
* 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

Primary outcomes:
measure: Maximum Severity of Oral Mucositis (World Health Organization (WHO) Grades 0/1, 2, 3, or 4)
timeFrame: at Day 32
measure: Incidence of Cataract Development or Progression at Month 12.
timeFrame: 12 months
Secondary outcomes:
measure: Incidence Ulcerative Mucositis (WHO Grades 2, 3, and 4)
timeFrame: at Day 32
measure: Duration of Ulcerative Mucositis (WHO Grades 2, 3, and 4)
timeFrame: at Day 32
measure: The Area Under the Curve (AUC) Was Calculated From the Patient-reported Outcome Mouth and Throat Soreness (MTS) Score.
timeFrame: at Day 32
measure: Incidence of Cataract Development or Progression (Change of ≥0.3 in Lens Opacities Classification System III (LOCS III Score)) at Month 6.
timeFrame: 6 Months
measure: Incidence of an Increase Posterior Subcapsular Cataract (P), Cortical Cataract (C) and Nuclear Opalescence (NO) at Month 6 and 12
timeFrame: at Month 6 and Month 12
measure: 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.
timeFrame: Months 6
measure: 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.
timeFrame: Months 12
measure: 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
timeFrame: Months 6
measure: 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.
timeFrame: Month 12
measure: Incidence of Adverse Events and Laboratory Abnormalities
timeFrame: at Day 32
measure: Overall Survival
timeFrame: During long-term follow up phase (maximum of 10 years)
measure: Progression Free Survival
timeFrame: During long-term follow up phase (maximum of 10 years)
measure: Time Death or Disease Progression
timeFrame: During long-term follow up phase (maximum of 10 years)
measure: Incidence of Second Primary Malignancies or Other Malignancies
timeFrame: During long-term follow up phase (maximum of 10 years)
Other outcomes:
Locations:
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
Study officials:
affiliation: Swedish Orphan Biovitrum AB
name: Kristina Timdahl, MD
role: STUDY_DIRECTOR
affiliation: Universitatsklinikum Leipzig, Leipzig, Germany
name: Dietger Niederwieser, Professor
role: PRINCIPAL_INVESTIGATOR
References: