Trial record 1 of 1 for:    NCT01503515
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Caspofungin Acetate, Fluconazole, or Voriconazole in Preventing Fungal Infections in Patients Following Donor Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01503515
First received: January 1, 2012
Last updated: February 5, 2014
Last verified: February 2014
  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. 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.


Condition Intervention Phase
Congenital Combined Immunodeficiency
Fungal Infection
Hematopoietic/Lymphoid Cancer
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: caspofungin acetate
Drug: fluconazole
Drug: voriconazole
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
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 Children's Oncology Group:

Primary Outcome Measures:
  • Development of proven or probable IFI defined according to criteria developed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) [ Time Frame: Up to 42 days following stem cell infusion ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be used to estimate the time to onset of proven/probable IFI for patients randomized to the 2 arms. Log rank test will be used to compare the incidence of IFI between the 2 randomized arms during the at-risk period.


Estimated Enrollment: 590
Study Start Date: March 2013
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (caspofungin acetate)
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
Other Names:
  • Cancidas
  • L-743,873
  • MK-0991
Other: laboratory biomarker analysis
Optional correlative studies
Active Comparator: Arm II (fluconazole or voriconazole)
Patients receive fluconazole IV over 1-2 hours QD or PO QD; or voriconazole IV over 1-2 hours QD or PO 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
Other Names:
  • Diflucan
  • FCZ
Drug: voriconazole
Given IV or PO
Other Names:
  • VCZ
  • Vfend
Other: laboratory biomarker analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. 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) II. 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) III. 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) IV. 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) V. To describe the effect that caspofungin and azoles have on the incidence and severity of acute graft-versus-host disease (GVHD). (Exploratory) VI. 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

Inclusion Criteria:

  • 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
  • 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 anidulafungin (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
  • Patients receiving treatment for an invasive fungal infection (IFI) are not eligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01503515

  Hide Study Locations
Locations
United States, California
Children's Oncology Group Recruiting
Arcadia, California, United States, 91006-3776
Contact: Christopher C. Dvorak    415-476-2188    dvorakc@peds.ucsf.edu   
Principal Investigator: Christopher C. Dvorak         
Loma Linda University Medical Center Recruiting
Loma Linda, California, United States, 92354
Contact: Antranik A. Bedros    909-558-3375      
Principal Investigator: Antranik A. Bedros         
Rady Children's Hospital - San Diego Recruiting
San Diego, California, United States, 92123
Contact: William D. Roberts    858-966-5934      
Principal Investigator: William D. Roberts         
University of California San Francisco Medical Center-Parnassus Recruiting
San Francisco, California, United States, 94143
Contact: Robert E. Goldsby    877-827-3222      
Principal Investigator: Robert E. Goldsby         
United States, Delaware
Alfred I duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Scott M. Bradfield    904-697-3529      
Principal Investigator: Scott M. Bradfield         
United States, Florida
Nemours Children's Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32207-8426
Contact: Scott M. Bradfield    904-697-3529      
Principal Investigator: Scott M. Bradfield         
All Children's Hospital Recruiting
Saint Petersburg, Florida, United States, 33701
Contact: Aleksandra Petrovic    727-767-2423    HamblinF@allkids.org   
Principal Investigator: Aleksandra Petrovic         
United States, Georgia
Children's Healthcare of Atlanta - Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Ann E. Haight    888-785-1112      
Principal Investigator: Ann E. Haight         
United States, Indiana
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Robert J. Fallon    317-274-2552      
Principal Investigator: Robert J. Fallon         
United States, Louisiana
Children's Hospital-Main Campus Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Lolie C. Yu    504-894-5377      
Principal Investigator: Lolie C. Yu         
United States, Michigan
C S Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: John E. Levine    800-865-1125      
Principal Investigator: John E. Levine         
Wayne State University Recruiting
Detroit, Michigan, United States, 48202
Contact: Roland L. Chu    313-576-9363      
Principal Investigator: Roland L. Chu         
Helen DeVos Children's Hospital at Spectrum Health Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: David S. Dickens    616-267-1925      
Principal Investigator: David S. Dickens         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Shakila P. Khan    507-538-7623      
Principal Investigator: Shakila P. Khan         
United States, Mississippi
University of Mississippi Medical Center Recruiting
Jackson, Mississippi, United States, 39216
Contact: Gail C. Megason    601-815-6700      
Principal Investigator: Gail C. Megason         
United States, Missouri
The Childrens Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Maxine L. Hetherington    816-234-3265      
Principal Investigator: Maxine L. Hetherington         
United States, Nebraska
Children's Hospital and Medical Center of Omaha Recruiting
Omaha, Nebraska, United States, 68114
Contact: Minnie Abromowitch    402-955-3949      
Principal Investigator: Minnie Abromowitch         
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Minnie Abromowitch    402-955-3949      
Principal Investigator: Minnie Abromowitch         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Stuart H. Gold    877-668-0683    cancerclinicaltrials@med.unc.edu   
Principal Investigator: Stuart H. Gold         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Susan G. Kreissman    888-275-3853      
Principal Investigator: Susan G. Kreissman         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Mark A. Ranalli    614-722-2708      
Principal Investigator: Mark A. Ranalli         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Rene Y. McNall-Knapp    405-271-4272    julie-traylor@ouhsc.edu   
Principal Investigator: Rene Y. McNall-Knapp         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David M. Barrett    215-590-2810      
Principal Investigator: David M. Barrett         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Adam Esbenshade    800-811-8480      
Principal Investigator: Adam Esbenshade         
United States, Texas
Methodist Children's Hospital of South Texas Recruiting
San Antonio, Texas, United States, 78229
Contact: Jaime Estrada    210-575-7000      
Principal Investigator: Jaime Estrada         
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Christopher Dvorak Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01503515     History of Changes
Other Study ID Numbers: ACCL1131, NCI-2012-00102, CDR0000721415, COG-ACCL1131, ACCL1131, COG-ACCL1131, ACCL1131, U10CA095861
Study First Received: January 1, 2012
Last Updated: February 5, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Mycoses
Immune System Diseases
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 July 29, 2014