A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Subjects With Acute Leukemias Undergoing HSCT - Full Text View

Sponsor:	Biovitrum
Information provided by:	Biovitrum
ClinicalTrials.gov Identifier:	NCT00460421

Purpose

20010133 is an open-label, dose escalation study in pediatric patients with acute leukemias receiving myelotoxic therapy (high dose etoposide, cyclophosphamide and total body irradiation [TBI]) followed by hematopoietic stem cell transplant (HSCT). The study will evaluate the safety and pharmacokinetics of palifermin in pediatric patients. Three doses (40 μg/kg/day, 60 μg/kg/day, and 80 μg/kg/day) are be evaluated in each age group (1 to 2, 3 to 11, and 12 to 16 years, respectively) using a conventional dose escalation design. Palifermin is administered for 3 consecutive days (Day -10 to Day -8, respectively) before the start of the conditioning regimen and for 3 consecutive days (Day 0 to Day +2) following HSCT. Patients will be enrolled simultaneously to each age group to identify a safe, well tolerated, efficacious dose in each age group. Patients will also be followed for secondary malignancies, progression-free survival (PFS) and overall survival (OS) for a maximum of 10 years

Condition	Intervention	Phase
Leukemia	Drug: Palifermin	Phase I

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Single Group Assignment, Safety Study
Official Title:	A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Pediatric Subjects With Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Childhood

Drug Information available for: Palifermin

U.S. FDA Resources

Further study details as provided by Biovitrum:

Primary Outcome Measures:

Safety- Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Approximately 1 month duration (Day -10 through Day +16) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of palifermin (eg, CL, Vss, t ½z) after the 1st and 3rd IV bolus injection for multiple dose levels [ Time Frame: Approximately 2 day duration (Day -10 and Day -8) ] [ Designated as safety issue: No ]
Incidence and severity of AEs, change in vital signs, and incidence of laboratory abnormalities [ Time Frame: Approximately 1 1/2 months duration (Through Day +30/End of Treatment) ] [ Designated as safety issue: No ]
Incidence of serum palifermin antibody formation [ Time Frame: Approximately 4 month duration (Through Day + 100 (+/- 40 days)) ] [ Designated as safety issue: Yes ]
Incidence of grade 3 and 4 OM as determined using the World Health Organization (WHO) Oral Toxicity grading scale [ Time Frame: Approximately 1 month duration (performed on Day - 10, -1, 0, 6, -3, -1, +1, +4, +6, + 8, +11, +13, +15) ] [ Designated as safety issue: No ]
Incidence of acute GVHD [ Time Frame: Approximately 4 month duration (Assessments take place through day +100 (+/- 40days) ] [ Designated as safety issue: Yes ]
Long-Term Follow-Up: Incidence of secondary malignancies [ Time Frame: Approximately 10 year duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and annually for a maximum of 10 years) ] [ Designated as safety issue: Yes ]
Long-Term Follow-Up: Progression Free Survival [ Time Frame: Approximately 10 year duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and annually for a maximum of 10 years) ] [ Designated as safety issue: Yes ]
Long-Term Follow-Up: Overall Survival [ Time Frame: Approximately 10 year duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and annually for a maximum of 10 years) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	54
Study Start Date:	August 2006
Estimated Study Completion Date:	April 2020
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
#1	Drug: Palifermin Palifermin will be administered as an IV bolus injection once daily for 3 consecutive days before the start of conditioning regimen and after HCST (Day -10, -9, -8 and Day 0, +1, +2 respectively).

Eligibility

Ages Eligible for Study:	1 Year to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

ALL or AML requiring HSCT
Age ≥ 1 and ≤ 16 years at screening
Lansky performance status > 60%
Candidate for allogeneic HSCT protocol:
- Adequate kidney function: Serum creatinine: ≤ 1.5 mg/dL or creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73m2
- Adequate liver function: Serum total bilirubin: ≤ 2.0 mg/dl; AST/ALT ≤ 4.0 x institutional upper limits of normal (IULN); Albumin ≥ 2 g/dL
- Adequate cardiac function: shortening fraction > 29% documented by echocardiogram, or ejection fraction ≥ 50% documented by multigated acquisition scan (MUGA).
- Adequate pulmonary function documented by corrected DLCO > 50% or oxygen saturation of ≥ 92% on room air if unable to perform pulmonary function tests
- Negative for human immunodeficiency virus (HIV), hepatitis C virus (HCV), human T cell lymphotropic virus (HTLV)
Identification of an HLA-compatible donor per institutional standards
Assent from a minor (if the child is capable of giving assent) per Department of Heath and Human Services (DHHS) guidelines listed in 21CFR 50.55 and local IRB standards.
Serum amylase and lipase: ≤ 1.2 x IULN
Negative serum/urine pregnancy test for females with childbearing potential within 4 days before administration of the first palifermin dose
Agreement by males and females of reproductive potential to use an effective means of contraception 30 days prior to enrollment through Day +30 (end of treatment)

Exclusion Criteria:

Prior treatment with palifermin or other keratinocyte growth factors
Received an investigational product or device, with the exception investigational stem cell separators, in another clinical trial within 30 days before enrollment.
Known to have a life threatening infection not responding well to treatment
Past history of veno-occlusive disease of the liver
Known sensitivity to any Escherichia coli-derived products with grade 3 to 4 allergies to L-asparaginase [grade 1 to 2 allergies to L-asparaginase will be allowed].
Receiving glutamine or any other medication to reduce the incidence of OM within 30 days before enrollment
Previous or concurrent malignancy other than entry diagnostic criteria and/or solid organ transplantation and/or treatment of congenital immunodeficiency
History of pancreatitis
Breastfeeding (giving)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460421

Contacts

Contact: Caroline Widlund, Bsc, R.N.

+46 8 697 2000

caroline.widlund@biovitrum.com

Locations

United States, Arizona
Arizona Cancer Center	Recruiting
Tucson, Arizona, United States
United States, California
Children´s Hospital	Active, not recruiting
Los Angeles, California, United States
Regents of University of California	Recruiting
Los Angeles, California, United States
Children´s Hospital of Orange	Recruiting
Orange, California, United States
Loma Linda University	Active, not recruiting
Loma Linda, California, United States
United States, Illinois
Children´s Memorial	Recruiting
Chicago, Illinois, United States
United States, Texas
University of Texas	Recruiting
Dallas, Texas, United States

Sponsors and Collaborators

Biovitrum

Investigators

Study Director:

Maarten de Chateau, MD, PhD

Biovitrum AB

More Information

No publications provided

Responsible Party:	Biovitrum AB (publ) ( Clinical Operations )
Study ID Numbers:	20010133
Study First Received:	April 12, 2007
Last Updated:	November 23, 2009
ClinicalTrials.gov Identifier:	NCT00460421 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Biovitrum:

Oral Mucositis
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Palifermin
Kepivance

Additional relevant MeSH terms:

Leukemia
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on February 08, 2010