Empirical Versus Preemptive Antifungal Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01288378
First received: February 1, 2011
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

RATIONALE: Caspofungin acetate may be effective in treating fungal infections in patients with acute myeloid leukemia or myelodysplastic syndrome who are receiving treatment for their cancer. It is not yet known whether caspofungin acetate is more effective when treatment starts after development of a fever or after the infection is shown in laboratory test, chest x-ray, or CT scan.

PURPOSE: This randomized phase III trial is studying the best time to start caspofungin acetate therapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed or in first relapse.


Condition Intervention Phase
Fungal Infection
Leukemia
Myelodysplastic Syndromes
Drug: caspofungin acetate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Empirical Versus Pre-emptive (Diagnostic-driven) Antifungal Therapy of Patients Treated for Haematological Malignancies or Receiving an Allogeneic Stem Cell Transplant. A Therapeutic Open Label Phase III Strategy Study of the EORTC Infectious Diseases and Leukemia Groups

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Overall survival at 42 days after randomization [ Time Frame: 6 weeks after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival at 84 days after randomization [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]
  • Development of proven or probable invasive fungal disease (IFD) during the 42 and 84 days following randomization [ Time Frame: during 84 days after randomization ] [ Designated as safety issue: Yes ]
  • Proper management according to allocated treatment arm (i.e., appropriate administration of caspofungin acetate in compliance to protocol, and compliance to the treatment strategy) during the 42 and 84 days after randomization [ Time Frame: during 84 days after randomization ] [ Designated as safety issue: No ]
  • Survival-free of fungal infection during the 42 and 84 days following randomization [ Time Frame: during 84 days after randomization ] [ Designated as safety issue: No ]
  • Safety (adverse event [AE] and serious adverse event [SAE]) as assessed by CTCAE criteria v4.0 [ Time Frame: during 84 days after randomization ] [ Designated as safety issue: Yes ]
  • Number of days under caspofungin treatment or under another antifungal treatment administered after caspofungin (evaluation will be done at day 42 and day 84 after randomization) [ Time Frame: at day 42 and day 84 after randomization ] [ Designated as safety issue: No ]
  • Costs related to the strategy for initiating and monitoring antifungal treatment during the 42 and 84 days following randomization [ Time Frame: during 84 days after randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 556
Study Start Date: March 2012
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Empirical
Empirical approach (fever driven) for starting antifungal therapy
Drug: caspofungin acetate
intravenous route, at a 70 mg loading dose on day 1 of antifungal therapy, followed by 50 mg once a day thereafter.
Experimental: Pre-emptive
Pre-emptive approach (diagnostic driven) for starting antifungal therapy
Drug: caspofungin acetate
intravenous route, at a 70 mg loading dose on day 1 of antifungal therapy, followed by 50 mg once a day thereafter.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

    • Newly diagnosed disease or disease in first relapse after hematological remission lasting for a minimum of 6 months AND meets one of the following criteria:

      • Starting remission-induction chemotherapy within 3 days prior to study randomization
      • Starting myeloablative conditioning regimen to prepare for a first allogeneic hematopoietic stem cell transplantation within 3 days prior to study randomization
  • Planning a hospital admission for the duration of the neutropenic phase (ANC < 0.5 x 10^9 /L)
  • Planning to receive oral or intravenous fluconazole for Candida prophylaxis at a dose of 400 mg/day

    • Fluconazole is discontinued during caspofungin acetate administration
  • No previous or current history of proven or probable invasive fungal disease (IFD)

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients muse use effective contraception during and for at least 3 months after completion of study therapy
  • No current clinical diagnosis of pneumonia
  • No serious, uncontrolled, concomitant disease or comorbidity that, in the opinion of the investigator, may compromise adherence to the study protocol
  • No history of allergy or any adverse reaction to echinocandin drugs (i.e., caspofungin acetate, micafungin, or anidulafungin)
  • No hypersensitivity to caspofungin active substance or to any of the excipients
  • No inadequately treated infection
  • No documented HIV infection
  • No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • No history of liver cirrhosis or severe hepatic insufficiency (i.e., Child Pugh Class C, D, or E)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No concurrent participation on another clinical trial using an investigational drug for infectious diseases
  • No other concurrent systemic antifungal therapy (oral or intravenous)
  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: NCT01288378

Contacts
Contact: Alice Preumont, PhD +30 2 774 15 10 alice.preumont@eortc.be

Locations
Belgium
A.Z. St. Jan Recruiting
Brugge, Belgium
Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet Recruiting
Brussels, Belgium
Cliniques Universitaires Saint-Luc Recruiting
Brussels, Belgium
U.Z. Gasthuisberg Recruiting
Leuven, Belgium
C.H.U. Sart-Tilman Recruiting
Liège, Belgium
Czech Republic
Masaryk University Recruiting
Brno, Czech Republic
France
CHU de Caen - Hopital Cote de Nacre Recruiting
Caen, France
C.H.U. Henri Mondor AP-HP Recruiting
Créteil, France
CHRU de Lille - Hopital Hurie Recruiting
Lille, France
CHU de Limoges - Hopital Dupuytren Recruiting
Limoges, France
Hopital Universitaire Hautepierre Recruiting
Strasbourg, France
Institut Gustave Roussy Recruiting
Villejuif, France
Germany
Universitaetsklinikum Freiburg Recruiting
Freiburg, Germany
Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II Recruiting
Wuerzburg, Germany
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands
Slovakia
National Cancer Institute Recruiting
Bratislava, Slovakia
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: J. Peter Donnelly Universitair Medisch Centrum St. Radboud - Nijmegen
Study Chair: Johan Maertens, MD U.Z. Gasthuisberg
Study Chair: Catherine Cordonnier, MD, PhD Centre Hospitalier Universitaire Henri Mondor
Study Chair: Tom Lodewyck AZ Sint-Jan
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01288378     History of Changes
Other Study ID Numbers: EORTC-65091-06093, 2010-020814-27, MK-0991-070
Study First Received: February 1, 2011
Last Updated: June 13, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic
Italy: Ethics Committee
Slovakia: State Institute for Drug Control
Croatia: Ministry of Health and Social Care
Turkey: Ministry of Health

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
fungal infection
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with del(5q)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary acute myeloid leukemia

Additional relevant MeSH terms:
Infection
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Mycoses
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Disease
Pathologic Processes
Miconazole
Antifungal Agents
Caspofungin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014