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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Cancer, Lymphoma, Leukemia

Intervention / Treatment
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* Drug: palifermin
* Radiation: Total Body Irradiation
* Drug: Cyclophosphamide
* Drug: Etoposide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Palifermin 60 µg/kg for 3 days<br>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<br>* Administered as one daily intravenous bolus.<br>* Other names: Recombinant Human Keratinocyte Growth Factor (rHuKGF);Radiation: Total Body Irradiation<br>* To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2<br>Drug: Etoposide<br>* Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.<br>* Other names: VP-16;Drug: Placebo<br>* Administered as one daily intravenous bolus.<br>|
| Experimental: Palifermin 180 μg/kg on Day -1<br>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<br>* Administered as one daily intravenous bolus.<br>* Other names: Recombinant Human Keratinocyte Growth Factor (rHuKGF);Radiation: Total Body Irradiation<br>* To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2<br>Drug: Etoposide<br>* Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.<br>* Other names: VP-16;Drug: Placebo<br>* Administered as one daily intravenous bolus.<br>|
| Experimental: Palifermin 180 μg/kg on Day -2<br>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<br>* Administered as one daily intravenous bolus.<br>* Other names: Recombinant Human Keratinocyte Growth Factor (rHuKGF);Radiation: Total Body Irradiation<br>* To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2<br>Drug: Etoposide<br>* Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.<br>* Other names: VP-16;Drug: Placebo<br>* Administered as one daily intravenous bolus.<br>|
| Experimental: Palifermin 180 μg/kg on Day -3<br>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<br>* Administered as one daily intravenous bolus.<br>* Other names: Recombinant Human Keratinocyte Growth Factor (rHuKGF);Radiation: Total Body Irradiation<br>* To be delivered before the administration of chemotherapy in 6, 8, or 10 fractions over 3 or 4 days.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide is administered at a total dose of 100 mg/kg given in 1 dose on Day -2<br>Drug: Etoposide<br>* Etoposide may be administered (optional) as a single intravenous infusion over 4 hours on the day after the last fTBI fraction.<br>* Other names: VP-16;Drug: Placebo<br>* Administered as one daily intravenous bolus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Oncology