Dose Escalation Study Of Palifermin in Pediatric Research Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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Mucositis is a well-known complication of both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). Many who suffer this disorder require total parental nutrition and intravenous narcotics for pain control. Palifermin (Kepivance[TM]) is a human keratinocyte growth factor that is produced by recombinant DNA technology in E. coli. Palifermin is a FDA-approved, commercially available pharmacologic agent that is manufactured by Amgen. As keratinocyte growth factor receptors have been found within the epithelium of gastric mucosa, the use of palifermin has been proven to decrease the frequency and duration of severe mucositis in adult studies. Whereas the appropriate dosing regimen has been determined for adults at 60mcg/kg/day, the dosing of palifermin has not been established in the pediatric setting. This initial pediatric study of palifermin will determine the maximum tolerated dose, evaluating the use of this agent at three dose levels, below, at, and above the recommended adult dose. Non-hematologic, life-threatening NCI grade IV or grade V toxicities definitely related to the administration of palifermin from the first infusion until day +6 after HSCT (post palifermin administration day +3) will comprise the safety endpoints of the study. The study is designed to evaluate palifermin at 3 dose levels. The study population will be recipients of either a matched family member donor or matched unrelated donor HSCT. The pharmacokinetics of palifermin at each dose level will be described to help determine the appropriate dose for future studies, which will evaluate efficacy

Detailed Description
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Secondary objectives of this study include exploring the pharmacoeconomics of palifermin in this particular patient population through an assessment of inpatient days, intravenous nutrition, and analgesia requirements within 100 days post-transplantation. We will also explore the research participants' rates of immune reconstitution, specifically T and B-lymphocytes and NK cells, within the first year of HSCT.

Official Title
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Phase I Study Of The Use Of Palifermin in Pediatric Research Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Oral Mucositis, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Palifermin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 2 years and less than 18 years of age. Diagnosis of a hematologic malignancy. Has not received a prior autologous or allogeneic HSCT. Is scheduled to receive either a matched family member or MUD bone marrow stem cell graft at St. Jude Children's Research Hospital. A matched family member donor is defined as a sibling matched at 5 or 6 HLA loci or another related donor matched at 6 HLA loci. Is scheduled to receive a myeloablative preparative regimen (cyclophosphamide/TBI based) prior to the infusion of the allogeneic graft. Cardiac shortening fraction greater than or equal to 25%. Serum creatinine is less than twice the upper limit of normal for age. Bilirubin less than 3.0 mg/dl. Aspartate transaminase (AST) less than 500 IU/ml. Alanine transaminase (ALT) less than 500 IU/ml. Amylase less than 1.5 times the upper limits of normal for age. Lipase less than 1.5 times the upper limits of normal for age. Forced vital capacity (FVC) greater than or equal to 40% of predicted value or pulse oximetry greater than or equal to 92% on room air. No known hypersensitivity to E coli-derived proteins or palifermin. No active or recent (within 30 days prior to enrollment) gastrointestinal bleeding. No active or recent (within 30 days prior to enrollment) oral ulcerations. No active fungal infection, bacteremia or viremia within two weeks prior to enrollment. Exclusion Criteria: Female - pregnant (negative serum or urine pregnancy test within 14 days prior to enrollment). Female - lactating.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>Palifermin 40 mcg/kg/day intravenous | Drug: Palifermin<br>* Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous<br>* Other names: Kepivance®;|
| Experimental: Dose Level 2<br>Palifermin 60 mcg/kg/day intravenous | Drug: Palifermin<br>* Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous<br>* Other names: Kepivance®;|
| Experimental: Dose Level 3<br>Palifermin 90 mcg/kg/day intravenous | Drug: Palifermin<br>* Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous<br>* Other names: Kepivance®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose and describe the toxicity profile of palifermin in pediatric research participants with hematologic malignancies undergoing first HSCT. |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mucositis, Oral, Hematopoietic Stem Cell Transplantation, Allogeneic Transplantation, Pharmacokinetics, Maximum Tolerated Dose