Palifermin in Preventing Oral Mucositis Caused by Chemotherapy and/or Radiation Therapy in Young Patients Undergoing Stem Cell Transplant

This study has been withdrawn prior to enrollment.
(Withdrawn due to lack of drug supply)
Sponsor:
Collaborator:
Information provided by:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00728585
First received: August 5, 2008
Last updated: May 30, 2013
Last verified: May 2013

August 5, 2008
May 30, 2013
January 2009
January 2009   (final data collection date for primary outcome measure)
Incidence of WHO grade 3 or 4 oral mucositis [ Time Frame: Up to day 32 ] [ Designated as safety issue: Yes ]
The incidence of WHO grade 3 or 4 mucositis, the palifermin and placebo groups, will be compared using a generalized Cochran-Mantel-Haenszel method for general association as the primary analysis. In addition, this outcome will be examined using a logistic regression model; both approaches will account for the randomization strata. Potential confounders will be examined using multiple logistic regression models.
Incidence of WHO grade 3 or 4 oral mucositis [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00728585 on ClinicalTrials.gov Archive Site
  • Incidence of adverse events and laboratory abnormalities of palifermin according to using Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 [ Time Frame: Up to 100 days post-HSCT ] [ Designated as safety issue: Yes ]
    Incidence of adverse events and laboratory abnormalities in the palifermin and placebo groups will be summarized for all study participants who receive at least one dose of study medication and also separately for autologous and allogeneic HSCT recipients using descriptive statistics. Time to neutrophil engraftment (first day of ANC 500/mm^3 for at least 2 consecutive days) will be examined in the palifermin and placebo groups and compared using the stratified log rank test. The incidence of serum anti-palifermin antibody formation will be summarized using descriptive statistics.
  • Long-term effects of palifermin on disease outcome and survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Long-term outcomes (progression free survival, overall survival and second malignancies) will be examined using Kaplan-Meier and cumulative incidence curves and the compared using the stratified log rank test. These outcomes will be summarized among all study participants and also separately for autologous and allogeneic HSCT recipient.
  • Duration of WHO grade 3 or 4 oral mucositis [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    Duration of grade 3 or 4 oral mucositis, duration of total parenteral nutrition (TPN) administration and total dose of parenteral opioid analgesic will be compared between groups using a stratified Wilcoxon test. Severity of mucositis according to the Oral Mucositis Assessment Scale (OMAS), modified Walsh mucositis scale, pain categorical rating scale and Oral Mucositis Daily Questionnaire (OMDQ) scales will be compared between groups using the area under the curve (AUC).
  • Daily OMAS scores [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
  • Daily modified Walsh mucositis scores [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
  • Daily pain categorical rating scales [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
  • Daily OMDQ [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    The AUC will be compared between groups using a stratified Wilcoxon test, in which stratum-specific rank tests are computed and then summed to obtain a combined test.
  • Incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents) [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    Incidence of parenteral opioid analgesic use TPN administration will be compared between groups using a generalized Cochran- Mantel-Haenszel test.
  • Incidence and duration of total parenteral nutrition administration [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    Incidence of parenteral opioid analgesic use TPN administration will be compared between groups using a generalized Cochran- Mantel-Haenszel test. If subjects are still receiving parenteral opioid analgesia or TPN on day 32, the subsequent stop date also will be collected.
  • Incidence of febrile neutropenia and invasive bacterial infections [ Time Frame: Up to day 32 ] [ Designated as safety issue: No ]
    The incidence of febrile neutropenia and invasive bacterial infections will be compared using a generalized Cochran-Mantel-Haenszel test.
  • Safety and tolerability of palifermin [ Designated as safety issue: Yes ]
  • Long-term disease outcome and survival [ Designated as safety issue: No ]
  • Duration of WHO grade 3 or 4 oral mucositis [ Designated as safety issue: No ]
  • Incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents) [ Designated as safety issue: No ]
  • Incidence and duration of total parenteral nutrition administration [ Designated as safety issue: No ]
  • Incidence of febrile neutropenia and invasive bacterial infections [ Designated as safety issue: No ]
  • Incidence of WHO grade 3 or 4 oral mucositis among allogeneic HSCT patients receiving methotrexate as GVHD prophylaxis [ Designated as safety issue: No ]
  • Incidence of acute and chronic GVHD after allogeneic HSCT [ Designated as safety issue: No ]
  • Health care utilization [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Palifermin in Preventing Oral Mucositis Caused by Chemotherapy and/or Radiation Therapy in Young Patients Undergoing Stem Cell Transplant
A Group-Wide Double-Blind Randomized Placebo-Controlled Trial of Palifermin to Prevent Chemotherapy and/or Radiotherapy Induced Oral Mucositis in Children Undergoing Autologous or Allogeneic Hematopoietic Stem Cell Transplantation

RATIONALE: Palifermin may help relieve or prevent oral mucositis caused by chemotherapy and radiation therapy in young patients undergoing stem cell transplant.

PURPOSE: This randomized phase II trial is studying palifermin to see how well it works compared with a placebo in preventing oral mucositis caused by chemotherapy and/or radiation therapy in young patients undergoing stem cell transplant.

OBJECTIVES:

Primary

  • To compare whether palifermin versus placebo administered to pediatric patients three days prior to conditioning and three days after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) is associated with a reduction in the incidence of WHO grade 3 or 4 oral mucositis.

Secondary

  • To evaluate the safety and tolerability of palifermin.
  • To evaluate the long-term effects of palifermin on disease outcome and survival.
  • To compare the incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents), and incidence and duration of total parenteral nutrition (TPN) administration in patients treated with these regimens.
  • To compare the incidence of febrile neutropenia and invasive bacterial infections in patients treated with these regimens.
  • To determine whether palifermin versus placebo reduces the incidence of WHO grade 3 or 4 oral mucositis among allogeneic HSCT pediatric patients receiving methotrexate as graft-versus-host disease (GVHD) prophylaxis.
  • To determine whether palifermin versus placebo reduces acute and chronic GVHD after allogeneic HSCT.
  • To describe health care utilization (hospitalization duration, and administration of antibiotics, TPN, nasogastric-, nasojejunal- or gastrostomy-administered enteral nutrition, and blood products) in pediatric patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to age in years (1 to 2 vs 3 to 11 vs 12 to 16), type of hematopoietic stem cell transplantation (HSCT) (autologous vs allogeneic), conditioning regimen (either total-body irradiation [TBI] or melphalan vs neither TBI nor melphalan). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive palifermin IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive palifermin IV on days 0, 1, and 2 after autologous or allogeneic HSCT.
  • Arm II: Patients receive placebo IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive placebo IV on days 0, 1, and 2 after autologous or allogeneic HSCT.

Blood samples are collected at baseline, 32 days, and 100 days after HSCT to evaluate the immunogenicity of palifermin. Oral mucositis is assessed at baseline, daily for 8 days prior to and 32 days after HSCT, or until oral mucositis has resolved by the WHO Mucositis Scale, Oral Mucositis Assessment Scale (OMAS), modified Walsh mucositis scale, Oral Mucositis Daily Questionnaire (OMDQ), and the pain categorical rating scale.

After completion of HSCT, patients are followed periodically for up to 10 years.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
  • Breast Cancer
  • Graft Versus Host Disease
  • Kidney Cancer
  • Leukemia
  • Lymphoma
  • Mucositis
  • Multiple Myeloma
  • Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Neuroblastoma
  • Ovarian Cancer
  • Sarcoma
  • Testicular Germ Cell Tumor
  • Biological: palifermin
    Given IV
    Other Names:
    • growth factor
    • recombinant human keratinocyte
    • Kepivance
    • keratinocyte growth factor
    • recombinant human
    • recombinant human keratinocyte growth factor
    • rhKGF
    • rhu keratinocyte growth factor
    • rHuKGF
  • Other: placebo
    Given IV
  • Experimental: Arm I
    Patients receive palifermin IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive palifermin IV on days 0, 1, and 2 after autologous or allogeneic hematopoietic stem cell transplantation.
    Intervention: Biological: palifermin
  • Placebo Comparator: Arm II
    Patients receive placebo IV once daily for 3 days prior to chemotherapy and/or radiotherapy in the absence of unacceptable toxicity. Patients then receive placebo IV on days 0, 1, and 2 after autologous or allogeneic hematopoietic stem cell transplantation.
    Intervention: Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
January 2009
January 2009   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Patients undergoing myeloablative autologous or allogeneic hematopoietic stem cell transplantation (HSCT) for any indication
  • Any type of myeloablative HSCT conditioning regimen allowed
  • Patients undergoing allogeneic HSCT may undergo 1 of the following types of donor stem cells:

    • HLA-matched sibling or parent
    • Partially matched family donor (mismatched for a single HLA locus [class I])
    • Fully matched unrelated marrow or peripheral blood stem cell donor
    • HLA-matched or partially mismatched (at least 4 of 6 match) cord blood (class I or II)

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No known sensitivity to any E. coli-derived products

    • Known grade 1 to 2 allergic reactions to asparaginase allowed
    • No prior grade 3-4 allergies to asparaginase or pegaspargase

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 30 days since prior and no concurrent treatment with any of the following therapies:

    • Oral cryotherapy
    • Glutamine as an oral supplement
    • Traumeel®
    • Gelclair®
    • Oral vancomycin paste
    • Low-level laser therapy
    • An investigational product or device in another clinical trial
  • No prior palifermin or other keratinocyte growth factors
  • No other concurrent cytotoxic drugs for conditioning or graft-vs-host disease prophylaxis

    • Intrathecal methotrexate or cytarabine for CNS involvement allowed
Both
1 Year to 16 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00728585
ACCL0521, COG-ACCL0521, CDR0000588622
No
Not Provided
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Lillian Sung, MD, PhD The Hospital for Sick Children
Children's Oncology Group
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP