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

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 to 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)


Eligibility Criteria:
Inclusion Criteria:

1. Acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) requiring HSCT
2. Age ≥ 1 and ≤ 16 years at screening
3. Lansky performance status \> 60%
4. Candidate for allogeneic HSCT protocol:

   * Adequate kidney function: Serum creatinine: ≤ 1.5 mg/dL or creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60 mL/min/1.73m2
   * Adequate liver function: Serum total bilirubin: ≤ 2.0 mg/dl; aspartate transaminase (AST)/alanine aminotransferase (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 lung diffusion capacity test (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)
5. Identification of an HLA-compatible donor per institutional standards
6. Assent from a minor (if the child is capable of giving assent) per Department of Health and Human Services (DHHS) guidelines listed in 21CFR 50.55 and local Institutional Review Board (IRB) standards.
7. Serum amylase and lipase: ≤ 1.2 x IULN
8. Negative serum/urine pregnancy test for females with childbearing potential within 4 days before administration of the first palifermin dose
9. 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:

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