Caspofungin Acetate, Fluconazole, or Voriconazole in Preventing Fungal Infections in Patients Following Donor Stem Cell Transplant
This study is not yet open for participant recruitment.
Verified December 2011 by National Cancer Institute (NCI)
Sponsor:
Children's Oncology Group
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01503515
First received: January 1, 2012
Last updated: NA
Last verified: December 2011
History: No changes posted
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Purpose
RATIONALE: Caspofungin acetate, fluconazole, and voriconazole may be effective in preventing fungal infections in patients following donor stem cell transplant. It is not yet known whether caspofungin acetate is more effective than fluconazole or voriconazole in preventing fungal infections in patients following donor stem cell transplant.
PURPOSE: This randomized phase II trial studies how well caspofungin acetate works compared to fluconazole or voriconazole in preventing fungal infections in patients following donor stem cell transplant.
| Condition | Intervention | Phase |
|---|---|---|
|
Fungal Infection Hematopoietic/Lymphoid Cancer Nonneoplastic Condition Unspecified Childhood Solid Tumor, Protocol Specific |
Drug: caspofungin acetate Drug: fluconazole Drug: voriconazole |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Masking: Open Label Primary Purpose: Supportive Care |
| Official Title: | A Phase III Open-Label Trial of Caspofungin vs. Azole Prophylaxis for Patients at High-Risk for Invasive Fungal Infections (IFI) Following Allogeneic Hematopoietic Cell Transplantation (HCT) |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Development of proven or probable invasive fungal infection (IFI) [ Designated as safety issue: No ]
| Estimated Enrollment: | 590 |
| Study Start Date: | December 2011 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic hematopoietic stem cell transplant (HSCT) and continuing until day 42 in the absence of invasive fungal infections or disease progression.
|
Drug: caspofungin acetate
Given IV
|
|
Active Comparator: Arm II
Patients receive fluconazole IV over 1-2 hours QD or orally (PO) QD; or voriconazole IV over 1-2 hours QD or PO twice daily (BID) beginning within 24 hours of allogeneic HSCT and continuing until day 42 in the absence of invasive fungal infections or disease progression.
|
Drug: fluconazole
Given IV or PO
Drug: voriconazole
Given IV or PO
|
Detailed Description:
OBJECTIVES:
Primary
- To determine if caspofungin acetate (caspofungin) is associated with a lower incidence of proven/probable invasive fungal infections (IFI) during the first 42 days following allogeneic hematopoietic cell transplantation (HCT) at high-risk for IFI compared with azole (fluconazole or voriconazole) prophylaxis.
Secondary
- To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 100 days following high-risk allogeneic HCT compared with azole (fluconazole or voriconazole) prophylaxis. (Exploratory)
- To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 42 and 100 days following high-risk allogeneic HCT compared with fluconazole prophylaxis. (Exploratory)
- To determine if caspofungin is associated with a lower incidence of proven/probable IFI during the first 42 and 100 days following high-risk allogeneic HCT compared with voriconazole prophylaxis. (Exploratory)
- To determine if caspofungin is associated with a superior fungal-free survival (FFS) (time to death or proven/probable IFI) at 42 and 100 days following high-risk allogeneic HCT compared with azole prophylaxis. (Exploratory)
- To describe the effect that caspofungin and azoles have on the incidence and severity of acute graft-versus-host disease (GVHD). (Exploratory)
- To determine the diagnostic performance characteristics of galactomannan and beta-D glucan testing in the setting of different anti-fungal prophylactic strategies for the early diagnoses of IFI following high-risk allogeneic HCT. (Exploratory)
- To create a DNA specimen bank in anticipation of the development of biology correlative studies exploring the relationship between IFI and single nucleotide polymorphisms (SNPs) of genes involved in immunity. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified by center's choice of azole (fluconazole vs voriconazole), age (≥ 12 years vs < 12 years), and type of transplant (umbilical cord blood [UCB] donor vs non-UCB donor with ex vivo T-cell depletion vs non-UCB donor with standard pharmacological graft-versus-host disease prophylaxis). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive caspofungin acetate IV over 1 hour once daily (QD) beginning within 24 hours of allogeneic hematopoietic stem cell transplantation (HSCT) and continuing until day 42 in the absence of invasive fungal infections or disease progression.
- Arm II: Patients receive fluconazole IV over 1-2 hours QD or orally (PO) QD; or voriconazole IV over 1-2 hours QD or PO twice daily (BID) beginning within 24 hours of allogeneic HSCT and continuing until day 42 in the absence of invasive fungal infections or disease progression.
After completion of study treatment, patients are followed up until days 100-114.
Eligibility| Ages Eligible for Study: | up to 20 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
- The patient must be undergoing allogeneic hematopoietic cell transplantation (HCT) for treatment of a malignancy, bone marrow failure syndrome, or congenital immunodeficiency
- The source for allogeneic stem cells (bone marrow, peripheral blood stem cells [PBSC], or umbilical cord blood) must be an unrelated donor or mismatched (≤ 7/8 at human leukocyte antigen [HLA]-A, B, C, and DR if bone marrow or PBSC; ≤ 5/6 at HLA-A, B, and DR if cord blood) family donor
- Patients with an elevated galactomannan level (≥ 0.5 Index) within 30 days prior to time of enrollment (if performed) must have a full evaluation for invasive aspergillosis (including a negative chest CT scan) during that time period to be eligible for enrollment
PATIENT CHARACTERISTICS:
- Age ≥ 3 months and < 21 years for patients receiving fluconazole as antifungal comparator
- Age ≥ 2 years and < 21 years for patients receiving voriconazole as the antifungal comparator
- ECOG scores of 0, 1 or 2 (Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL OR serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 month to < 6 months of age)
- 0.5 mg/dL (6 months to < 1 year of age)
- 0.6 mg/dL (1 to < 2 years of age)
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age (unless the increase in bilirubin is attributable to Gilbert syndrome)
- SGOT (AST) or SGPT (ALT) < 2.5 times ULN for age
- Patients with a history of proven or probable invasive mold infection are not eligible
- Patients with an incompletely treated invasive yeast infection are not eligible
- Patients with a history of an idulafungin (echinocandin) or azole (fluconazole or voriconazole) hypersensitivity are not eligible
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Patients receiving treatment for an invasive fungal infection (IFI) are not eligible
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Peter C. Adamson, Children's Oncology Group - Group Chair Office |
| ClinicalTrials.gov Identifier: | NCT01503515 History of Changes |
| Other Study ID Numbers: | CDR0000721415, COG-ACCL1131 |
| Study First Received: | January 1, 2012 |
| Last Updated: | January 1, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
fungal infection unspecified childhood solid tumor, protocol specific hematopoietic/lymphoid cancer congenital combined immunodeficiency |
Additional relevant MeSH terms:
|
Mycoses Fluconazole Voriconazole Caspofungin Echinocandins Antifungal Agents |
Anti-Infective Agents Therapeutic Uses Pharmacologic Actions 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013