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

NCT00434161 | Completed Phase 3 Results

• 1 other identifier: 20050219
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Palifermin; KGF; Clinical Trial; Oncology; Oral Mucositis; Multiple Myeloma; Cataract

Outcome Measures

Primary Outcomes (2)

• Maximum Severity of Oral Mucositis (World Health Organization (WHO) Grades 0/1, 2, 3, or 4)

  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.

  at Day 32

• Incidence of Cataract Development or Progression at Month 12.

  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).

  12 months

Secondary Outcomes (14)

• Incidence Ulcerative Mucositis (WHO Grades 2, 3, and 4)

  at Day 32

• Duration of 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 Cataract Development or Progression (Change of ≥0.3 in Lens Opacities Classification System III (LOCS III Score)) at Month 6.

  6 Months

• 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

Study Arms (3)

Palifermin before only

ACTIVE COMPARATOR

Subjects received palifermin before-high dose chemotherapy (total 3 doses) and matched placebo after-high dose chemotherapy (total 3 doses)

Drug: Palifermin before only

Placebo (suger pill)

PLACEBO COMPARATOR

Subjects received matched placebo before- and after-high dose chemotherapy

Drug: Placebo

Palifermin before and after

ACTIVE COMPARATOR

Subjects received palifermin before- and after-high dose chemotherapy (total of 6 doses)

Drug: Palifermin before and after

Interventions

Palifermin before only DRUG

One bolus IV injection at 60 μg/kg/day, on Days 6, 5 \& 4 days before-high dose chemotherapy and one bolus IV injection at 60 μg/kg/day of matched placebo on days 0, 1 \& 2 days after-high dose chemotherapy. Minimum of 4 days between before-chemotherapy and after-transplantation dosing.

Also known as: Kepivance

Palifermin before only

Placebo DRUG

One bolus IV injection at 60 μg/kg/day of matched placebo on Days 6, 5 \& 4 (before-high dose chemotherapy) and on Days 0, 1 \& 2 (after-high dose chemotherapy). Minimum of 4 days between pre-chemotherapy and post-transplantation dosing.

Placebo (suger pill)

Palifermin before and after DRUG

One bolus IV injection at 60 μg/kg/day, on Days 6, 5 \& 4 (before-high dose chemotherapy) and on Days 0, 1 \& 2 (after-high dose chemotherapy). Minimum of 4 days between before-chemotherapy and after-transplantation dosing.

Also known as: Kepivance

Palifermin before and after

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (1)

Universitatsklinikum Leipzig

Leipzig, Germany

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Stomatitis; Cataract

Interventions

Fibroblast Growth Factor 7

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Mouth Diseases; Stomatognathic Diseases; Lens Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Medical Director
• Organization: Swedish Orphan Biovitrum AB

clinical@sobi.com

+4686972000

Study Officials

• Kristina Timdahl, MD

  Swedish Orphan Biovitrum AB

  STUDY DIRECTOR

• Dietger Niederwieser, Professor

  Universitatsklinikum Leipzig, Leipzig, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2007
• First Posted: February 12, 2007
• Study Start: December 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: May 1, 2012
• Last Updated: March 30, 2015
• Results First Posted: March 10, 2015

Record last verified: 2015-03

Locations

DE (1)