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

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier:
NCT00109031
First received: April 22, 2005
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention Phase
Cancer
Lymphoma
Leukemia
Drug: palifermin
Radiation: Total Body Irradiation
Drug: Cyclophosphamide
Drug: Etoposide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • Number of Participants With Severe Oral Mucositis (WHO Grade 3 and 4) [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From the first day of study drug administration through Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to Day 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 47
Study Start Date: January 2005
Study Completion Date: December 2010
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Palifermin 60 µg/kg for 3 days
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
Administered as one daily intravenous bolus.
Other Names:
  • Kepivance
  • Recombinant Human Keratinocyte Growth Factor (rHuKGF)
Radiation: Total Body Irradiation
To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.
Drug: Cyclophosphamide
Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2
Drug: Etoposide
Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.
Other Name: VP-16
Drug: Placebo
Administered as one daily intravenous bolus.
Experimental: Palifermin 180 μg/kg on Day −1
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
Administered as one daily intravenous bolus.
Other Names:
  • Kepivance
  • Recombinant Human Keratinocyte Growth Factor (rHuKGF)
Radiation: Total Body Irradiation
To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.
Drug: Cyclophosphamide
Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2
Drug: Etoposide
Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.
Other Name: VP-16
Drug: Placebo
Administered as one daily intravenous bolus.
Experimental: Palifermin 180 μg/kg on Day −2
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
Administered as one daily intravenous bolus.
Other Names:
  • Kepivance
  • Recombinant Human Keratinocyte Growth Factor (rHuKGF)
Radiation: Total Body Irradiation
To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.
Drug: Cyclophosphamide
Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2
Drug: Etoposide
Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.
Other Name: VP-16
Drug: Placebo
Administered as one daily intravenous bolus.
Experimental: Palifermin 180 μg/kg on Day −3
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
Administered as one daily intravenous bolus.
Other Names:
  • Kepivance
  • Recombinant Human Keratinocyte Growth Factor (rHuKGF)
Radiation: Total Body Irradiation
To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.
Drug: Cyclophosphamide
Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2
Drug: Etoposide
Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.
Other Name: VP-16
Drug: Placebo
Administered as one daily intravenous bolus.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00109031

Sponsors and Collaborators
Swedish Orphan Biovitrum
Amgen
Investigators
Study Director: MD Amgen
  More Information

No publications provided

Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT00109031     History of Changes
Obsolete Identifiers: NCT00126529, NCT00965692
Other Study ID Numbers: 20040212
Study First Received: April 22, 2005
Results First Received: January 24, 2014
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Swedish Orphan Biovitrum:
Cancer
Oncology

Additional relevant MeSH terms:
Leukemia
Lymphoma
Stomatitis
Mucositis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mouth Diseases
Stomatognathic Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cyclophosphamide
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 14, 2014