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

NCT00701688 | Completed Phase 1

• 1 other identifier: PALSCT
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Oral Mucositis; Hematopoietic Stem Cell Transplantation

Keywords

Mucositis, Oral; Hematopoietic Stem Cell Transplantation; Allogeneic Transplantation; Pharmacokinetics; Maximum Tolerated Dose

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Dose Level 1

EXPERIMENTAL

Palifermin 40 mcg/kg/day intravenous

Drug: Palifermin

Dose Level 2

EXPERIMENTAL

Palifermin 60 mcg/kg/day intravenous

Drug: Palifermin

Dose Level 3

EXPERIMENTAL

Palifermin 90 mcg/kg/day intravenous

Drug: Palifermin

Interventions

Palifermin DRUG

Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous

Also known as: Kepivance®

Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Female - pregnant (negative serum or urine pregnancy test within 14 days prior to enrollment).
• Female - lactating.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Stomatitis

Interventions

Fibroblast Growth Factor 7

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Ashok Srinivasan, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2008
• First Posted: June 19, 2008
• Study Start: September 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: February 1, 2012
• Last Updated: March 23, 2012

Record last verified: 2012-03

Locations

US (1)