Clinical trial NCT00728585: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Gastrointestinal Mucositis
Malignant Neoplasm
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-08-06
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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:

  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

Primary outcomes:
measure: Incidence of WHO grade 3 or 4 oral mucositis
timeFrame: Up to day 32
Secondary outcomes:
measure: Incidence of adverse events and laboratory abnormalities of palifermin according to using Common Terminology Criteria for Adverse Events (CTCAE) v 3.0
timeFrame: Up to 100 days post-HSCT
measure: Long-term effects of palifermin on disease outcome and survival
timeFrame: Up to 10 years
measure: Duration of WHO grade 3 or 4 oral mucositis
timeFrame: Up to day 32
measure: Daily OMAS scores
timeFrame: Up to day 32
measure: Daily modified Walsh mucositis scores
timeFrame: Up to day 32
measure: Daily pain categorical rating scales
timeFrame: Up to day 32
measure: Daily OMDQ
timeFrame: Up to day 32
measure: Incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents)
timeFrame: Up to day 32
measure: Incidence and duration of total parenteral nutrition administration
timeFrame: Up to day 32
measure: Incidence of febrile neutropenia and invasive bacterial infections
timeFrame: Up to day 32
Other outcomes:
Locations:
Study officials:
affiliation: Children's Oncology Group
name: Lillian Sung
role: PRINCIPAL_INVESTIGATOR
References: