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

Primary Purpose

Gastrointestinal Mucositis, Malignant Neoplasm

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Palifermin
Placebo
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Gastrointestinal Mucositis

Eligibility Criteria

1 Year - 16 Years (Child)All SexesDoes not accept healthy volunteers

Criteria:

  • 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:

    1. HLA-matched sibling or parent
    2. Partially matched family donor (mismatched for a single HLA locus [class I])
    3. Fully matched unrelated marrow or peripheral blood stem cell donor
    4. HLA-matched or partially mismatched (at least 4 of 6 match) cord blood (class I or II)
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No known sensitivity to any E. coli-derived products

    1. Known grade 1 to 2 allergic reactions to asparaginase allowed
    2. No prior grade 3-4 allergies to asparaginase or pegaspargase
  • More than 30 days since prior and no concurrent treatment with any of the following therapies:

    1. Oral cryotherapy
    2. Glutamine as an oral supplement
    3. Traumeel
    4. Gelclair
    5. Oral vancomycin paste
    6. Low-level laser therapy
    7. 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)
  • Not pregnant or nursing

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Arm I (palifermin)

    Arm II (placebo)

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Incidence of WHO grade 3 or 4 oral mucositis
    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
    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
    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
    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
    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
    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
    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
    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)
    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
    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
    The incidence of febrile neutropenia and invasive bacterial infections will be compared using a generalized Cochran-Mantel-Haenszel test.

    Full Information

    First Posted
    August 5, 2008
    Last Updated
    August 3, 2018
    Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00728585
    Brief Title
    Palifermin in Preventing Oral Mucositis Caused by Chemotherapy and/or Radiation Therapy in Young Patients Undergoing Stem Cell Transplant
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2013
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Withdrawn
    Study Start Date
    March 13, 2008 (Actual)
    Primary Completion Date
    May 8, 2009 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Children's Oncology Group
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    5. Study Description

    Brief Summary
    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. Palifermin may help relieve or prevent oral mucositis caused by chemotherapy and radiation therapy in young patients undergoing stem cell transplant.
    Detailed Description
    PRIMARY OBJECTIVES: I. 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 OBJECTIVES: I. To evaluate the safety and tolerability of palifermin. II. To evaluate the long-term effects of palifermin on disease outcome and survival. III. 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. IV. To compare the incidence of febrile neutropenia and invasive bacterial infections in patients treated with these regimens. TERTIARY OBJECTIVES: I. 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. II. To determine whether palifermin versus placebo reduces acute and chronic GVHD after allogeneic HSCT. III. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastrointestinal Mucositis, Malignant Neoplasm

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm I (palifermin)
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Arm II (placebo)
    Arm Type
    Placebo Comparator
    Arm Description
    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 Type
    Drug
    Intervention Name(s)
    Palifermin
    Other Intervention Name(s)
    Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth Factor, rhKGF, rhu Keratinocyte Growth Factor
    Intervention Description
    Given IV
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Other Intervention Name(s)
    placebo therapy, PLCB, sham therapy
    Intervention Description
    Given IV
    Primary Outcome Measure Information:
    Title
    Incidence of WHO grade 3 or 4 oral mucositis
    Description
    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.
    Time Frame
    Up to day 32
    Secondary Outcome Measure Information:
    Title
    Incidence of adverse events and laboratory abnormalities of palifermin according to using Common Terminology Criteria for Adverse Events (CTCAE) v 3.0
    Description
    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.
    Time Frame
    Up to 100 days post-HSCT
    Title
    Long-term effects of palifermin on disease outcome and survival
    Description
    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.
    Time Frame
    Up to 10 years
    Title
    Duration of WHO grade 3 or 4 oral mucositis
    Description
    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).
    Time Frame
    Up to day 32
    Title
    Daily OMAS scores
    Description
    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.
    Time Frame
    Up to day 32
    Title
    Daily modified Walsh mucositis scores
    Description
    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.
    Time Frame
    Up to day 32
    Title
    Daily pain categorical rating scales
    Description
    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.
    Time Frame
    Up to day 32
    Title
    Daily OMDQ
    Description
    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.
    Time Frame
    Up to day 32
    Title
    Incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents)
    Description
    Incidence of parenteral opioid analgesic use TPN administration will be compared between groups using a generalized Cochran- Mantel-Haenszel test.
    Time Frame
    Up to day 32
    Title
    Incidence and duration of total parenteral nutrition administration
    Description
    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.
    Time Frame
    Up to day 32
    Title
    Incidence of febrile neutropenia and invasive bacterial infections
    Description
    The incidence of febrile neutropenia and invasive bacterial infections will be compared using a generalized Cochran-Mantel-Haenszel test.
    Time Frame
    Up to day 32

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Year
    Maximum Age & Unit of Time
    16 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Criteria: 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) 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 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) Not pregnant or nursing
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Lillian Sung
    Organizational Affiliation
    Children's Oncology Group
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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