LeukemiaPhase 1NCT00460421
A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Subjects With Acute Leukemias Undergoing HSCT
A Phase 1 study testing Palifermin, Total Body irradiation and Chemotherapy in people with Leukemia, run by Swedish Orphan Biovitrum at 7 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 16 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Palifermin, Total Body irradiation and Chemotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 7 sitesUnited States
- Study dates
- Aug 2006to May 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Children´s Memorial
Chicago, Illinois
University of Texas
Dallas, Texas
Loma Linda University
Loma Linda, California
Children´s Hospital
Los Angeles, California
Regents of University of California
Los Angeles, California
Children´s Hospital of Orange
Orange, California
Arizona Cancer Center
Tucson, Arizona
About this 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)
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
- Being tested
- Palifermin, Total Body irradiation, Chemotherapy
- Keywords
- Oral Mucositis, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Palifermin, Kepivance
- Medical subject headings
- Leukemia, Stomatitis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaliferminDrug
Also called Kepivance
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).
Total Body irradiationRadiation
ChemotherapyDrug
High dose etoposide, Cyclophosphamide
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Palifermin; Radiation: Total Body irradiation; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 1 month duration (Day -10 through Day +16)
Secondary outcomes (12)
Incidence of Serum Palifermin Antibody Formation
The percentage of participants developing palifermin antibodies during the study was assessed.
Measured: Approximately 4 month duration (Through Day + 100 (+/- 40 days))
Incidence of Severe Adverse Events (AEs)
The percentage of participants with a severe AE during the study was assessed.
Measured: Approximately 1 1/2 months duration (Through Day +30/End of Treatment)
Incidence of Laboratory Abnormalities
The percentage of participants with a laboratory value outside the normal ranges during the study.
Measured: 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
Clearence was estimated as dose divided by the area under serum concentration-time curve from time zero to infinity where the dose was given in amount palifermin actually administered.
Measured: Day -10
Pharmacokinetics of Palifermin, Volume of Distribution at Steady State (Vss) After the 1st IV Bolus Injection for Multiple Dose Levels
Measured: Day -10
Pharmacokinetics of Palifermin, Terminal Half-life (t½,z) After the 1st IV Bolus Injection for Multiple Dose Levels
The terminal half-life was calculated as ln(2)/lambda,z where lambda,z was estimated using at least three quantifiable serum concentrations of the terminal log-linear phase.
Measured: Day -10
Pharmacokinetics of Palifermin, t½,z After the 3rd IV Bolus Injection for Multiple Dose Levels
The terminal half-life was calculated as ln(2)/lambda,z where lambda,z was estimated using at least three quantifiable serum concentrations of the terminal log-linear phase.
Measured: Day -8
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
The AUC was estimated using the linear/log trapezoidal method for AUC0-tau from time zero to the end of the dosing interval (24 hours (hrs) post-dose)
Data collected at time points: 0, 2 minutes (min), 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6, hrs, 10, hrs and 24 hrs post-dose.
Measured: Day -10
Pharmacokinetics of Palifermin, AUCtau After the 3rd IV Bolus Injection for Multiple Dose Levels
The AUC was estimated using the linear/log trapezoidal method for AUC0-tau from time zero to the end of the dosing interval (24 hours (hrs) post-dose)
Data collected at time points: 0, 2 minutes (min), 15 min, 30 min, 60 min, 2 hrs, 4 hrs, 6, hrs, 10, hrs and 24 hrs post-dose.
Measured: Day -8
Long-Term Follow-Up: Incidence of Secondary Malignancies
Measured: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)
Long-Term Follow-Up: Progression Free Survival
Progression free survival (PFS) was defined as the number of days between the date of first investigational product administration and the date when physical or radiological evidence of disease progression is determined or death (regardless of cause)
Measured: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)
Long-Term Follow-Up: Overall Survival
Overall survival was defined as the number of days from the date of first investigational product administration to the date of death (regardless of cause)
Measured: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2007 (estimated)
- Study startAug 2006
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Maarten de Chateau, MD, PhD, Study director, Swedish Orphan Biovitrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00460421
- Sponsor's protocol ID
- 20010133
- Status last verified
- Nov 2014
- First submitted
- 12 Apr 2007
- Last updated
- 5 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00460421
- Acronym / sponsor ID
- 20010133
- Conditions
- Leukemia
- Keywords
- Oral Mucositis, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Palifermin, Kepivance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 16 Apr 2007 (estimated)
- Results
- Posted 3 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Palifermin Dose Escalation | Experimental | Drug: Palifermin, Radiation: Total Body irradiation, Drug: ChemotherapyA 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). |
Who may qualify
- Ages
- 1 year to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (14 listed)
- 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:
- Identification of an HLA-compatible donor per institutional standards
Key exclusion criteria (9 listed)
- 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].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaliferminAlso: KepivancePalifermin 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). | Drug | Palifermin Dose Escalation |
| Total Body irradiation | Radiation | Palifermin Dose Escalation |
| ChemotherapyHigh dose etoposide, Cyclophosphamide | Drug | Palifermin Dose Escalation |
Primary outcome
Incidence of Dose Limiting Toxicities (DLTs)
Time frame: Approximately 1 month duration (Day -10 through Day +16)
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.
12 secondary outcomes
Incidence of Serum Palifermin Antibody Formation
Time frame: Approximately 4 month duration (Through Day + 100 (+/- 40 days))
Incidence of Severe Adverse Events (AEs)
Time frame: Approximately 1 1/2 months duration (Through Day +30/End of Treatment)
Incidence of Laboratory Abnormalities
Time frame: 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
Time frame: Day -10
Pharmacokinetics of Palifermin, Volume of Distribution at Steady State (Vss) After the 1st IV Bolus Injection for Multiple Dose Levels
Time frame: Day -10
Pharmacokinetics of Palifermin, Terminal Half-life (t½,z) After the 1st IV Bolus Injection for Multiple Dose Levels
Time frame: Day -10
Pharmacokinetics of Palifermin, t½,z After the 3rd IV Bolus Injection for Multiple Dose Levels
Time frame: Day -8
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
Time frame: Day -10
Pharmacokinetics of Palifermin, AUCtau After the 3rd IV Bolus Injection for Multiple Dose Levels
Time frame: Day -8
Long-Term Follow-Up: Incidence of Secondary Malignancies
Time frame: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)
Long-Term Follow-Up: Progression Free Survival
Time frame: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)
Long-Term Follow-Up: Overall Survival
Time frame: Up to 4 years duration (Assessments performed on months 6, 9, 12 (+/- 30 Days) for the first year and then annually)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maarten de Chateau, MD, PhD study director
Swedish Orphan Biovitrum
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Palifermin, Total Body irradiation and Chemotherapy in people with Leukemia, run by Swedish Orphan Biovitrum at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose Limiting Toxicities (DLTs) (time frame: Approximately 1 month duration (Day -10 through Day +16)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2014.