Phase 1
Completed N=27
A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Subjects With Acute Leukemias Undergoing HSCT
Source: ClinicalTrials.gov NCT00460421 ↗Enrolled (actual)
27
Serious AEs
18.5%
Results posted
Jul 2012
Primary outcomePrimary: Incidence of Dose Limiting Toxicities (DLTs) — 0; 0; 0 percentage of participants
Summary
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)
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Dose Limiting Toxicities (DLTs) |
0; 0; 0 | — |
| SECONDARY Incidence of Serum Palifermin Antibody Formation |
0; 0; 0 | — |
| SECONDARY Incidence of Severe Adverse Events (AEs) |
100; 100; 100 | — |
| SECONDARY Incidence of Laboratory Abnormalities |
100; 100; 100 | — |
| SECONDARY Pharmacokinetics of Palifermin, Clearence (CL) After the 1st Intravenous (IV) Bolus Injection for Multiple Dose Levels |
1954.84; 2164.87; 3932.30 | — |
| SECONDARY Pharmacokinetics of Palifermin, Volume of Distribution at Steady State (Vss) After the 1st IV Bolus Injection for Multiple Dose Levels |
2552.79; 5134.84; 8580.91 | — |
| SECONDARY Pharmacokinetics of Palifermin, Terminal Half-life (t½,z) After the 1st IV Bolus Injection for Multiple Dose Levels |
2.91; 3.05; 3.68 | — |
| SECONDARY Pharmacokinetics of Palifermin, t½,z After the 3rd IV Bolus Injection for Multiple Dose Levels |
3.40; 3.89; 2.99 | — |
| SECONDARY Pharmacokinetics of Palifermin, Area Under the Concentration Time Curve From Zero to the End of the Dosing Interval (AUCtau) After the 1st IV Bolus Injection for Multiple Dose Levels |
16.54; 18.14; 38.44 | — |
| SECONDARY Pharmacokinetics of Palifermin, AUCtau After the 3rd IV Bolus Injection for Multiple Dose Levels |
18.32; 17.97; 34.74 | — |
| SECONDARY Long-Term Follow-Up: Incidence of Secondary Malignancies |
0; 11; 0 | — |
| SECONDARY Long-Term Follow-Up: Progression Free Survival |
NA; NA; NA; 36 | — |
| SECONDARY Long-Term Follow-Up: Overall Survival |
NA; NA; NA; 36 | — |
Eligibility Criteria
Inclusion Criteria
- Acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (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 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)
- Identification of an HLA-compatible donor per institutional standards
- 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.
- 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 oral mucositis (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)
Data sourced from ClinicalTrials.gov (NCT00460421). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.