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
- 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.
- 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
- 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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
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.
Up to day 32
Lillian Sung, MD, PhD
The Hospital for Sick Children