Empirical Versus Preemptive Antifungal Therapy

NCT01288378 | Completed Phase 3 DMC

• 3 other identifiers: EORTC-65091-060932010-020814-27MK-0991-070
• Study Type: interventional
• Target: 556
• Locations: 6 countries
• Sites: 16

Brief Summary

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.

Conditions

Fungal Infection; Leukemia; Myelodysplastic Syndromes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival at 42 days after randomization

  6 weeks after randomization

Secondary Outcomes (7)

• Overall survival at 84 days after randomization

  12 weeks after randomization

• Development of proven or probable invasive fungal disease (IFD) during the 42 and 84 days following randomization

  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

  during 84 days after randomization

• Survival-free of fungal infection during the 42 and 84 days following randomization

  during 84 days after randomization

• Safety (adverse event [AE] and serious adverse event [SAE]) as assessed by CTCAE criteria v4.0

  during 84 days after randomization

Study Arms (2)

Empirical

ACTIVE COMPARATOR

Empirical approach (fever driven) for starting antifungal therapy

Drug: caspofungin acetate

Pre-emptive

EXPERIMENTAL

Pre-emptive approach (diagnostic driven) for starting antifungal therapy

Drug: caspofungin acetate

Interventions

caspofungin acetate DRUG

intravenous route, at a 70 mg loading dose on day 1 of antifungal therapy, followed by 50 mg once a day thereafter.

Empirical; Pre-emptive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (16)

A.Z. St. Jan

Bruges, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Hôpitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, Belgium

Location

U.Z. Gasthuisberg

Leuven, Belgium

Location

C.H.U. Sart-Tilman

Liège, Belgium

Location

Masaryk University

Brno, Czechia

Location

CHU de Caen - Hopital Cote de Nacre

Caen, France

Location

C.H.U. Henri Mondor AP-HP

Créteil, France

Location

CHRU de Lille - Hopital Hurie

Lille, France

Location

CHU de Limoges - Hopital Dupuytren

Limoges, France

Location

Hopital Universitaire Hautepierre

Strasbourg, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II

Würzburg, Germany

Location

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

Location

National Cancer Institute

Bratislava, Slovakia

Location

Related Publications (1)

• Maertens J, Lodewyck T, Donnelly JP, Chantepie S, Robin C, Blijlevens N, Turlure P, Selleslag D, Baron F, Aoun M, Heinz WJ, Bertz H, Racil Z, Vandercam B, Drgona L, Coiteux V, Llorente CC, Schaefer-Prokop C, Paesmans M, Ameye L, Meert L, Cheung KJ, Hepler DA, Loeffler J, Barnes R, Marchetti O, Verweij P, Lamoth F, Bochud PY, Schwarzinger M, Cordonnier C; Infectious Diseases Group and the Acute Leukemia Group of the European Organization for Research and Treatment of Cancer. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023 Feb 18;76(4):674-682. doi: 10.1093/cid/ciac623.

  PMID: 35906831 DERIVED

MeSH Terms

Conditions

Mycoses; Leukemia; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Congenital Abnormalities

Interventions

Caspofungin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Echinocandins; Peptides, Cyclic

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2011
• First Posted: February 2, 2011
• Study Start: March 1, 2012
• Primary Completion: April 4, 2019
• Study Completion: April 4, 2019
• Last Updated: December 11, 2023

Record last verified: 2023-12

Locations

CZ (1); FR (6); BE (5); DE (2); NL (1); SL (1)