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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00109031
• Other study ID #: 20040212
• Status: Completed
• Phase: Phase 3
• First received: April 22, 2005
• Last updated: September 12, 2014
• Start date: January 2005
• Est. completion date: December 2010

Study information

• Verified date: September 2014
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Other known NCT identifiers

• NCT00126529
• NCT00965692

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: December 2010
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• Cancer
• Leukemia
• Lymphoma
• Stomatitis

Intervention

Drug:
• palifermin
Administered as one daily intravenous bolus.

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
• Etoposide
Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.
• Placebo
Administered as one daily intravenous bolus.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum	Amgen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Up to Day 28	No
Secondary	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.	From the first day of study drug administration through Day 28	No
Secondary	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.	Up to Day 28	No
Secondary	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.	Up to Day 28	No
Secondary	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.	Up to Day 28	No
Secondary	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.	Up to Day 28	No