Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

This study has been completed.
Sponsor:
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT00336531
First received: June 11, 2006
Last updated: November 17, 2008
Last verified: November 2008
  Purpose

The purpose of this study is to investigate whether the prophylactic use of itraconazole is a better option than empirical use of itraconazole in the management (prevention and treatment) of fungal infection associated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation in children with high-risk solid tumor.


Condition Intervention Phase
Neuroblastoma
Brain Tumor
Retinoblastoma
Wilms Tumor
Mycoses
Drug: itraconazole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Clinical Study to Evaluate the Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Pediatric Solid Tumors

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Presence/absence of documented fungal infection [ Time Frame: until post transplant day 30 ] [ Designated as safety issue: No ]
  • Presence/absence of clinical fungal infection [ Time Frame: until post transplant day 30 ] [ Designated as safety issue: No ]
  • Total duration of high fever [ Time Frame: until post transplant day 30 ] [ Designated as safety issue: No ]
  • Total duration of antibiotic treatment [ Time Frame: until post transplant day 30 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: April 2006
Study Completion Date: October 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: itraconazole
    2.5 mg/kg twice daily for the first two days --> once daily
Detailed Description:

With the advance of chemoradiotherapy, survival of patients, especially children, with malignant disease has improved. However, prognosis is still poor with conventional chemotherapy if patients have an advanced or high-risk tumor at diagnosis. Outcome in advanced or high-risk pediatric solid tumor such as advanced neuroblastoma, high-risk brain tumor, or recurrent pediatric solid tumor is still not satisfactory with conventional chemotherapy. In this context, investigators have explored the possible efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in patients with high-risk or relapsed pediatric solid tumor. Efficacy of HDCT and ASCT has been well demonstrated in high-risk neuroblastoma, high-risk brain tumor, and recurrent pediatric solid tumors. Therefore, now, HSCT and ASCT is the most important treatment modality in the treatment of a variety of pediatric solid tumors poorly responding to conventional chemotherapy.

However, although HDCT and ASCT has improved the survival of patients with high-risk tumor, a variety of clinical issues associated with HDCT and ASCT are present causing significant morbidity and even mortality. The most frequent cause of morbidity associated with HDCT and ASCT is infection. Once high-dose myeloablative chemotherapeutic agents are administered, most hematopoietic cells in bone marrow die and prolonged marrow aplasia is unavoidable even after autologous hematopoietic stem cells infusion because it takes time for infused stem cells to reconstitute sufficient hematopoietic function. In addition, high-dose chemotherapy results in severe gastrointestinal mucosal damage which facilitates bacterial and/or fungal infection via damaged mucosal barrier. Therefore, infection is a major cause of morbidity and mortality associated with HDCT and ASCT. Common pathogens associated with infection during HDCT and ASCT are bacteria and fungi.

To reduce the chance of infection and therefore, to reduce the morbidity and mortality from severe infection, various prophylactic antibiotics including antibacterial, antifungal, and antiviral agents have been used according to standard guideline in allogeneic stem cell transplantation. However, in autologous transplantation for solid tumor in which hematologic recovery is rapid and immune suppression is less severe than allogeneic transplantation, there is no standard guideline for the use of prophylactic antibiotics whereas infection is the most important cause of morbidity. Standard guideline for the use of prophylactic antifungal agent is also not available. While some institutes use anti-fungal agent prophylactically, others use antifungal agent empirically only when neutropenic fever persist despite of empirical use of antibacterial agents.

HDCT in pediatric solid tumor is generally more intensive, and therefore, usually cause more severe mucositis than that in adult tumor. Severe mucositis facilitates fungal infection via damaged mucosal barrier (mainly by Candida species). Therefore, use of prophylactic anti-fungal agent may reduce the morbidity and mortality associated with HDCT and ASCT in pediatric solid tumor. However, there is no randomized clinical study to evaluate the efficacy of prophylactic use of anti-fungal agent to date.

Itraconazole is one of newly developed antifungal agents and many physicians started to use itraconazole as first-line antifungal agent in the management of neutropenic fever in immunocompromised patients. However, the efficacy of prophylactic itraconazole has not been established in children with solid tumor, especially who receive HDCT and ASCT.

In this context, we are going to evaluate the efficacy of prophylactic use of itraconazole in children with high-risk solid tumors during HDCT and ASCT. "Prophylactic" group will be treated with itraconazole once ANC fall below 500/uL regardless of infection and "Empirical" group will be treated with itraconazole only when high fever persists despite of treatment with first-line anti-bacterial agents.

  Eligibility

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with high risk solid tumors who are going to receive high dose chemotherapy and autologous hematopoietic stem cell transplantation

Exclusion Criteria:

  • Significant organ toxicity (National Cancer Institute [NCI] grade > 2) prior to high dose chemotherapy and autologous hematopoietic stem cell transplantation
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00336531

Locations
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: KiWoong Sung, MD, PhD Samsung Medical Center
  More Information

No publications provided by Samsung Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ki Woong Sung, Samsng Medical Center
ClinicalTrials.gov Identifier: NCT00336531     History of Changes
Other Study ID Numbers: 2006-02-069
Study First Received: June 11, 2006
Last Updated: November 17, 2008
Health Authority: Korea: Food and Drug Administration

Keywords provided by Samsung Medical Center:
prophylactic itraconazole
Relapsed pediatric solid tumors
Embryonal brain tumor

Additional relevant MeSH terms:
Neuroblastoma
Brain Neoplasms
Wilms Tumor
Retinoblastoma
Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn
Retinal Neoplasms
Eye Neoplasms
Eye Diseases

ClinicalTrials.gov processed this record on September 22, 2014