Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003879

Trial Description

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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

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

OBJECTIVES:

Primary

- To compare empirical approach (i.e., fever driven) versus preemptive approach (i.e.,
diagnostic driven), for starting antifungal therapy with caspofungin acetate, in
patients with acute myeloid leukemia or myelodysplastic syndrome who are starting
chemotherapy (for attaining remission induction) or myeloablation (to prepare for an
allogeneic hematopoietic stem cell transplantation) for newly diagnosed disease or
disease in first relapse.

Secondary

- To evaluate clinical validity and utility of a standardized Aspergillus PCR assay.

- To evaluate clinical validity and utility of beta-D-glucan.

- To determine the occurrence of single nucleotide polymorphisms (SNPs) and the
predictive value of SNPs for identifying patients at higher risk of developing invasive
fungal infection.

OUTLINE: This is a multicenter study. Patients are stratified according to institution,
prior allogeneic stem cell transplantation (yes vs no), and type of air flow (laminar air
flow vs high-efficiency particulate air). Patients are randomized to 1 of 2 treatment arms.

- Arm A (Empirical approach): Patients start caspofungin acetate treatment when one of
the following criteria are met:

- Presence of unexplained persistent fever refractory to 4 full days of
broad-spectrum antibacterial therapy with any of the following regimens either
alone or in combination with an aminoglycoside or a glycopeptide:

- Ceftazidime

- Cefepime

- Piperacillin/tazobactam

- Imipenem-cilastatin

- Meropenem

- New fever occurring > 2 days after resolution of a first fever while continuing
broad-spectrum antibacterial therapy as defined above for which no obvious cause
has been documented and fungal infection cannot be excluded Patients receive
caspofungin acetate IV once daily. Treatment continues until neutrophil recovers.

- Arm B (Preemptive approach): Patients start caspofungin acetate treatment when at least
one of the following criteria* are met:

- Single plasma or serum galactomannan ELISA with index > 0.5

- New pulmonary infiltrate on chest x-ray and IFD cannot be readily excluded

- New dense well-circumscribed lesions with or without a halo sign, on a CT scan,
consistent with IFD

- Aspergillus sp. recovered by culture from sputum Patients receive caspofungin
acetate IV once daily. Treatment continues until neutrophil recovers.

NOTE: *These criteria are not sufficient to warrant preemptive caspofungin acetate therapy:
skin lesions evocative of IFD, sinusitis or orbititis, hepatosplenic abscesses
(hypodensities on CT scan), or unexplained persistent fever for more than 7 days or
recurrent fever whatever its duration.

All patients undergo blood sample collection periodically for the detection of galactomannan
and beta-D-glucan and for the detection of single nucleotide polymorphisms. Some patients
undergo blood sample collection for the detection of Aspergillus via PCR. An economic
evaluation is performed for cost-effectiveness analysis.

After completion of study treatment, patients are followed periodically.

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Organizational Data

  •   DRKS00003879
  •   2012/07/16
  •   2011/02/01
  •   yes
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Secondary IDs

  •   2010-020814-27 
  •   NCT01288378  (ClinicalTrials.gov)
  •   EORTC-65091-06093  (European Organization for Research and Treatment of Cancer - EORTC)
  •   2010-020814-27 
  •   MK-0991-070 
  •   4037613 
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Health Condition or Problem studied

  •   Fungal Infection
  •   Leukemia
  •   Myelodysplastic Syndromes
  •   C92.0 -  Acute myeloid leukaemia
  •   D46 -  Myelodysplastic syndromes
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Interventions/Observational Groups

  •   Drug: caspofungin acetate
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Supportive care
  •   Parallel
  •   III
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Primary Outcome

- Overall survival at 42 days after randomization; time frame: 6 weeks after randomization

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Secondary Outcome

- Overall survival at 84 days after randomization; time frame: 12 weeks after randomization
- Development of proven or probable invasive fungal disease (IFD) during the 42 and 84 days following randomization; time frame: during 84 days after randomization
- 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
- Survival-free of fungal infection during the 42 and 84 days following randomization; time frame: during 84 days after randomization
- Safety (adverse event [AE] and serious adverse event [SAE]) as assessed by CTCAE criteria v4.0; time frame: during 84 days after randomization
- 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
- 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

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Countries of Recruitment

  •   Belgium
  •   France
  •   Netherlands
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Locations of Recruitment

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Recruitment

  •   Planned
  •   2012/03/31
  •   556
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion 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)

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Exclusion Criteria

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Addresses

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    • European Organisation for Research and Treatment of Cancer - EORTC
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    • Universitair Medisch Centrum St. Radboud - Nijmegen
    • J. Peter Donnelly 
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    • Alice Preumont, PhD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   8
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.