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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00701688
First received: June 17, 2008
Last updated: March 22, 2012
Last verified: March 2012
  Purpose

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


Condition Intervention Phase
Oral Mucositis
Hematopoietic Stem Cell Transplantation
Drug: Palifermin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Of The Use Of Palifermin in Pediatric Research Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • To determine the maximum tolerated dose and describe the toxicity profile of palifermin in pediatric research participants with hematologic malignancies undergoing first HSCT. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: September 2007
Study Completion Date: February 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 1
Palifermin 40 mcg/kg/day intravenous
Drug: Palifermin
Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous
Other Name: Kepivance®
Experimental: Dose Level 2
Palifermin 60 mcg/kg/day intravenous
Drug: Palifermin
Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous
Other Name: Kepivance®
Experimental: Dose Level 3
Palifermin 90 mcg/kg/day intravenous
Drug: Palifermin
Dose level 1 40 mcg/kg/day intravenous Dose level 2 60 mcg/kg/day intravenous Dose level 3 90 mcg/kg/day intravenous
Other Name: Kepivance®

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00701688

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Ashok Srinivasan, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00701688     History of Changes
Other Study ID Numbers: PALSCT
Study First Received: June 17, 2008
Last Updated: March 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Mucositis, Oral
Hematopoietic Stem Cell Transplantation
Allogeneic Transplantation
Pharmacokinetics
Maximum Tolerated Dose

Additional relevant MeSH terms:
Mucositis
Stomatitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases

ClinicalTrials.gov processed this record on October 01, 2014