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

NCT00460421 | Completed Phase 1 Results DMC

• 1 other identifier: 20010133
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 7

Brief 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)

Conditions

Leukemia

Keywords

Oral Mucositis; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Palifermin; Kepivance

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicities (DLTs)

  A DLT is appearance of side effects during treatment severe enough to prevent further increase in dosage or strength of treatment agent, or to prevent continuation of treatment at any dosage level. A DLT was defined as: Grade 3 or 4 AE \[based on Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) v3.0\] considered by the investigator to be related to palifermin with the exceptions: Grade 3 erythema, pruritus or rash that resolves within 7 days of the last dose of palifermin. The percentage of particiapnts with a DLT during the study was assessed.

  Approximately 1 month duration (Day -10 through Day +16)

Secondary Outcomes (12)

• Incidence of Serum Palifermin Antibody Formation

  Approximately 4 month duration (Through Day + 100 (+/- 40 days))

• Incidence of Severe Adverse Events (AEs)

  Approximately 1 1/2 months duration (Through Day +30/End of Treatment)

• Incidence of Laboratory Abnormalities

  Approximately 1 1/2 months duration (Through Day +30/End of Treatment)

• Pharmacokinetics of Palifermin, Clearence (CL) After the 1st Intravenous (IV) Bolus Injection for Multiple Dose Levels

  Day -10

• Pharmacokinetics of Palifermin, Volume of Distribution at Steady State (Vss) After the 1st IV Bolus Injection for Multiple Dose Levels

  Day -10

Study Arms (1)

Palifermin Dose Escalation

EXPERIMENTAL

A 3 dose escalation design. Sucessive cohorts of patient (9 patients per group) will each be administered Palifermin as an IV bolus injection (40, 60 or 80 µg) once daily for 3 consecutive days before the start of conditioning regimen (chemotherapy and total body irradiation) and after HCST (Day -10, -9, -8 and Day 0, +1, +2 respectively).

Drug: Palifermin; Radiation: Total Body irradiation; Drug: Chemotherapy

Interventions

Palifermin DRUG

Palifermin will be administered as an IV bolus injection (40, 60 or 80 µg/kg/day)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).

Also known as: Kepivance

Palifermin Dose Escalation

Total Body irradiation RADIATION

Palifermin Dose Escalation

Chemotherapy DRUG

High dose etoposide, Cyclophosphamide

Palifermin Dose Escalation

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (7)

Arizona Cancer Center

Tucson, Arizona, United States

Location

Loma Linda University

Loma Linda, California, United States

Location

Children´s Hospital

Los Angeles, California, United States

Location

Regents of University of California

Los Angeles, California, United States

Location

Children´s Hospital of Orange

Orange, California, United States

Location

Children´s Memorial

Chicago, Illinois, United States

Location

University of Texas

Dallas, Texas, United States

Location

MeSH Terms

Conditions

Leukemia; Stomatitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Fibroblast Growth Factor 7; Whole-Body Irradiation; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Mouth Diseases; Stomatognathic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Radiotherapy; Therapeutics; Investigative Techniques

Limitations and Caveats

The original protocol included a long term follow-up (LTFU) phase up to 10 years. This was reduced in a protocol amendment to up to the time when the last enrolled subject had completed the day +100 follow-up.

Results Point of Contact

• Title: Medical Program Director
• Organization: Swedish Orphan Biovitrum

clinical@sobi.com

+46 8 697 20 00

Study Officials

• Maarten de Chateau, MD, PhD

  Swedish Orphan Biovitrum AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2007
• First Posted: April 16, 2007
• Study Start: August 1, 2006
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: December 5, 2014
• Results First Posted: July 3, 2012

Record last verified: 2014-11

Locations

US (7)