search
Back to results

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

Primary Purpose

Cancer, Lymphoma, Leukemia

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
palifermin
Total Body Irradiation
Cyclophosphamide
Etoposide
Placebo
Sponsored by
Swedish Orphan Biovitrum
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cancer focused on measuring Cancer, Oncology

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: Cancer other than those specified in inclusion criteria above (except: adequately treated basal cell carcinoma of the skin) 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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Active Comparator

    Experimental

    Experimental

    Experimental

    Arm Label

    Palifermin 60 µg/kg for 3 days

    Palifermin 180 μg/kg on Day -1

    Palifermin 180 μg/kg on Day -2

    Palifermin 180 μg/kg on Day -3

    Arm Description

    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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Duration of Severe Oral Mucositis (WHO Grade 3 and 4)
    The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.
    Area Under the Curve (AUC) of Mouth and Throat Soreness Score
    The Oral Mucositis Daily Questionnaire (OMDQ) is a self-reported tool that evaluates overall health, mouth and throat soreness (MTS) and activity limitations due to MTS. The OMDQ was completed once daily beginning with the first day of study drug administration through Day 28. The area under the curve of mouth and throat soreness score was assessed from the question "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). A higher value in MTS AUC indicates worse self-assessed MTS.
    Number of Participants With Parenteral or Transdermal Opioid Analgesic Use
    Includes nonprophylactic intravenous opioid analgesics (fentanyl, morphine, morphine sulphate, hydromorphone, meperidine) and transdermal opioid analgesics (fentanyl patch) for the indication of oral mucositis and dysphagia.
    Number of Participants With WHO Grades 2, 3 or 4 Oral Mucositis
    Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) daily during hospitalization and daily thereafter until 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.
    Duration of WHO Grade 2, 3 or 4 Oral Mucositis
    The duration of grade 2, 3 or 4 oral mucositis (OM) was calculated as the number of days from the onset of grade 2, 3 or 4 OM (first time a WHO grade 2, 3 or 4 was observed) to the day when WHO grade 2 - 4 OM was resolved (first time WHO grade less than 2 was observed after last WHO grade 2, 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 2, 3 or 4 during the study. OM was evaluated 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.
    Number of Participants With WHO Grade 4 Oral Mucositis
    Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) daily during hospitalization and daily thereafter until 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.

    Full Information

    First Posted
    April 22, 2005
    Last Updated
    September 12, 2014
    Sponsor
    Swedish Orphan Biovitrum
    Collaborators
    Amgen
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00109031
    Brief Title
    Palifermin for the Reduction of Oral Mucositis in Single-dose Evaluation (PROMISE)
    Official Title
    A Randomized, Blinded, Active-control Trial of Palifermin (rHuKGF) to Evaluate Oral Mucositis in Subjects With Hematologic Malignancies Undergoing Fractionated Total Body Irradiation (fTBI) and High Dose Chemotherapy With Autologous Peripheral Blood Progenitor Cell (PBPC) Transplantation
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2014
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2005 (undefined)
    Primary Completion Date
    February 2006 (Actual)
    Study Completion Date
    December 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Swedish Orphan Biovitrum
    Collaborators
    Amgen

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cancer, Lymphoma, Leukemia
    Keywords
    Cancer, Oncology

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    47 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Palifermin 60 µg/kg for 3 days
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Palifermin 180 μg/kg on Day -1
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Palifermin 180 μg/kg on Day -2
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Palifermin 180 μg/kg on Day -3
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    palifermin
    Other Intervention Name(s)
    Kepivance, Recombinant Human Keratinocyte Growth Factor (rHuKGF)
    Intervention Description
    Administered as one daily intravenous bolus.
    Intervention Type
    Radiation
    Intervention Name(s)
    Total Body Irradiation
    Intervention Description
    To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Intervention Description
    Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2
    Intervention Type
    Drug
    Intervention Name(s)
    Etoposide
    Other Intervention Name(s)
    VP-16
    Intervention Description
    Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Administered as one daily intravenous bolus.
    Primary Outcome Measure Information:
    Title
    Number of Participants With Severe Oral Mucositis (WHO Grade 3 and 4)
    Description
    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.
    Time Frame
    Up to Day 28
    Secondary Outcome Measure Information:
    Title
    Duration of Severe Oral Mucositis (WHO Grade 3 and 4)
    Description
    The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.
    Time Frame
    Up to Day 28
    Title
    Area Under the Curve (AUC) of Mouth and Throat Soreness Score
    Description
    The Oral Mucositis Daily Questionnaire (OMDQ) is a self-reported tool that evaluates overall health, mouth and throat soreness (MTS) and activity limitations due to MTS. The OMDQ was completed once daily beginning with the first day of study drug administration through Day 28. The area under the curve of mouth and throat soreness score was assessed from the question "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). A higher value in MTS AUC indicates worse self-assessed MTS.
    Time Frame
    From the first day of study drug administration through Day 28
    Title
    Number of Participants With Parenteral or Transdermal Opioid Analgesic Use
    Description
    Includes nonprophylactic intravenous opioid analgesics (fentanyl, morphine, morphine sulphate, hydromorphone, meperidine) and transdermal opioid analgesics (fentanyl patch) for the indication of oral mucositis and dysphagia.
    Time Frame
    Up to Day 28
    Title
    Number of Participants With WHO Grades 2, 3 or 4 Oral Mucositis
    Description
    Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) daily during hospitalization and daily thereafter until 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.
    Time Frame
    Up to Day 28
    Title
    Duration of WHO Grade 2, 3 or 4 Oral Mucositis
    Description
    The duration of grade 2, 3 or 4 oral mucositis (OM) was calculated as the number of days from the onset of grade 2, 3 or 4 OM (first time a WHO grade 2, 3 or 4 was observed) to the day when WHO grade 2 - 4 OM was resolved (first time WHO grade less than 2 was observed after last WHO grade 2, 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 2, 3 or 4 during the study. OM was evaluated 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.
    Time Frame
    Up to Day 28
    Title
    Number of Participants With WHO Grade 4 Oral Mucositis
    Description
    Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) daily during hospitalization and daily thereafter until 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.
    Time Frame
    Up to Day 28

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: Cancer other than those specified in inclusion criteria above (except: adequately treated basal cell carcinoma of the skin) 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)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs