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This study has been withdrawn prior to enrollment.
(Withdrawn due to lack of drug supply)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
  Purpose

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.


Condition Intervention Phase
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
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 0
Study Start Date: January 2009
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Other: placebo
Given IV

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   1 Year to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00728585

Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Lillian Sung, MD, PhD The Hospital for Sick Children
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00728585     History of Changes
Other Study ID Numbers: ACCL0521, COG-ACCL0521, CDR0000588622
Study First Received: August 5, 2008
Last Updated: May 30, 2013
Health Authority: Unspecified

Keywords provided by Children's Oncology Group:
mucositis
graft versus host disease
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
juvenile myelomonocytic leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
childhood myelodysplastic syndromes
de novo myelodysplastic syndromes
disseminated neuroblastoma
previously treated childhood rhabdomyosarcoma
previously treated myelodysplastic syndromes
recurrent Wilms tumor and other childhood kidney tumors
recurrent childhood rhabdomyosarcoma
recurrent neuroblastoma
recurrent malignant testicular germ cell tumor
secondary myelodysplastic syndromes
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Graft vs Host Disease
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Neuroblastoma
Ovarian Neoplasms
Stomatitis
Neoplasms, Germ Cell and Embryonal
Mucositis
Sarcoma
Neoplasms by Site
Breast Diseases
Skin Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 29, 2014