Palifermin for the Reduction of Oral Mucositis in Single-dose Evaluation (PROMISE)

NCT00109031 | Completed Phase 3 Results DMC

• 1 other identifier: 20040212
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate whether palifermin (rHuKGF) administered as a single dose is non-inferior to 3 consecutive doses of palifermin in reducing the incidence of severe oral mucositis (World Health Organization \[WHO\] grade 3 and 4).

Conditions

Cancer; Lymphoma; Leukemia

Keywords

Cancer; Oncology

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Severe Oral Mucositis (WHO Grade 3 and 4)

  Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) daily during hospitalization and daily thereafter until severe OM returned to grade ≤ 2. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.

  Up to Day 28

Secondary Outcomes (6)

• Duration of Severe Oral Mucositis (WHO Grade 3 and 4)

  Up to Day 28

• Area Under the Curve (AUC) of Mouth and Throat Soreness Score

  From the first day of study drug administration through Day 28

• Number of Participants With Parenteral or Transdermal Opioid Analgesic Use

  Up to Day 28

• Number of Participants With WHO Grades 2, 3 or 4 Oral Mucositis

  Up to Day 28

• Duration of WHO Grade 2, 3 or 4 Oral Mucositis

  Up to Day 28

Study Arms (4)

Palifermin 60 µg/kg for 3 days

ACTIVE COMPARATOR

Palifermin 60 µg/kg plus placebo to match the total volume equivalent to a 180 µg/kg dose on the 3 days prior to fractionated total body irradiation (fTBI) and palifermin 60 µg/kg on Days 0, 1 and 2 after peripheral blood progenitor cell transplantation (PBPC). Participants also received conditioning therapy with fTBI and cyclophosphamide/etoposide prior to PBPC transplantation on Day 0.

Drug: palifermin; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Placebo

Palifermin 180 μg/kg on Day -1

EXPERIMENTAL

Palifermin 180 μg/kg on Day -1 and matched placebo on Days -2 and -3 prior to fTBI, and palifermin 60 μg/kg on Days 0, 1, and 2 after PBPC. Participants also received conditioning therapy with fTBI and cyclophosphamide/etoposide prior to PBPC transplantation on Day 0.

Drug: palifermin; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Placebo

Palifermin 180 μg/kg on Day -2

EXPERIMENTAL

Palifermin 180 μg/kg on Day -2 and placebo on Days -1 and -3 prior to fTBI, and palifermin 60 μg/kg on Days 0, 1, and 2 after PBPC. Participants also received conditioning therapy with fTBI and cyclophosphamide/etoposide prior to PBPC transplantation on Day 0.

Drug: palifermin; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Placebo

Palifermin 180 μg/kg on Day -3

EXPERIMENTAL

Palifermin 180 μg/kg on Day -3 and placebo on Days -1 and -2 prior to fTBI, and palifermin 60 μg/kg on Days 0, 1, and 2 after PBPC. Participants also received conditioning therapy with fTBI and cyclophosphamide/etoposide prior to PBPC transplantation on Day 0.

Drug: palifermin; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Placebo

Interventions

palifermin DRUG

Administered as one daily intravenous bolus.

Also known as: Kepivance, Recombinant Human Keratinocyte Growth Factor (rHuKGF)

Palifermin 180 μg/kg on Day -1; Palifermin 180 μg/kg on Day -2; Palifermin 180 μg/kg on Day -3; Palifermin 60 µg/kg for 3 days

Total Body Irradiation RADIATION

To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.

Palifermin 180 μg/kg on Day -1; Palifermin 180 μg/kg on Day -2; Palifermin 180 μg/kg on Day -3; Palifermin 60 µg/kg for 3 days

Cyclophosphamide DRUG

Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2

Palifermin 180 μg/kg on Day -1; Palifermin 180 μg/kg on Day -2; Palifermin 180 μg/kg on Day -3; Palifermin 60 µg/kg for 3 days

Etoposide DRUG

Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.

Also known as: VP-16

Palifermin 180 μg/kg on Day -1; Palifermin 180 μg/kg on Day -2; Palifermin 180 μg/kg on Day -3; Palifermin 60 µg/kg for 3 days

Placebo DRUG

Administered as one daily intravenous bolus.

Palifermin 180 μg/kg on Day -1; Palifermin 180 μg/kg on Day -2; Palifermin 180 μg/kg on Day -3; Palifermin 60 µg/kg for 3 days

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Subjects with: non-Hodgkin's lymphoma, Hodgkin's disease, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, or multiple myeloma
• Minimum of 1.5 x 10\^6 CD34+ cells/kg cryopreserved and to be transplanted.

You may not qualify if:

• Prior bone marrow or peripheral blood stem cell transplantation - Negatively selected (purged) stem cell product - Current active infection or oral mucositis
• Congestive heart failure as defined by New York Heart Association class III or IV.
• History of or current diagnosis of pancreatitis
• Inadequate renal function (serum creatinine greater than 1.5x the upper limit of normal per the institutional guidelines)
• Inadequate liver function (direct bilirubin greater than 1.5x the upper limit of normal, aspartate aminotransferase (AST) greater than 3x upper limit of normal and/or alanine aminotransferase (ALT) greater than 3x upper limit of normal per the institutional guidelines)
• Inadequate pulmonary function as measured by a corrected diffusion capacity of carbon monoxide (DLCO) less than 50% of predicted.
• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s)

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead
• Amgen: collaborator

MeSH Terms

Conditions

Neoplasms; Lymphoma; Leukemia

Interventions

Fibroblast Growth Factor 7; Whole-Body Irradiation; Cyclophosphamide; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Hans Olivecrona, MD PhD
• Organization: Swedish Orphan Biovitrum

hans.olivecrona@sobi.com

+46 8 697 20 00

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 22, 2005
• First Posted: April 25, 2005
• Study Start: January 1, 2005
• Primary Completion: February 1, 2006
• Study Completion: December 1, 2010
• Last Updated: September 15, 2014
• Results First Posted: September 15, 2014

Record last verified: 2014-09