RATIONALE: Liposomal amphotericin B may be effective in controlling fever and granulocytopenia. It is not yet known which regimen of liposomal amphotericin B is more effective in treating cancer patients who have these conditions.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of liposomal amphotericin B in treating granulocytopenia and fever in cancer patients.

Condition	Treatment or Intervention	Phase
Kidney Disease Breast Cancer Endocrine Cancer Gastrointestinal Cancer Hematopoietic and Lymphoid Cancer Central Nervous System Cancer	Drug: amphotericin B liposomal  Procedure: antifungal therapy  Procedure: infection prophylaxis/management  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy and side effects of amphotericin B-liposomal formulation initiated 72-84 hours vs 144-156 hours after onset of a febrile episode in cancer patients with granulocytopenia and persistent unexplained fever refractory to antibacterials.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to antifungal prophylaxis (yes vs no) and type of underlying condition. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive amphotericin B-liposomal formulation IV over 1 hour on day 3 of febrile neutropenia.
• Arm II: Patients receive amphotericin B-liposomal formulation IV over 1 hour on day 6 of febrile neutropenia. Treatment continues until signs and symptoms of the fungal infection appear or febrile neutropenia has resolved. Persistently neutropenic patients receive treatment for at least 10 days or until another cause of infection is determined.

Patients are followed weekly for 3 weeks.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Hematologic malignancy or solid tumor
• Must be undergoing remission induction and/or consolidation therapy for hematologic malignancy only OR
• Must be undergoing allogeneic or autologous bone marrow transplantation
• Granulocyte count less than 500/mm^3 and profound granulocytopenia expected to last for greater than 5 days
• Fever (greater than 38.5 degrees C) refractory for greater than 72 hours and less than 84 hours to broad spectrum antimicrobials, after exclusion of current bacterial, fungal, viral, parasitic, and mycobacterial infections
• Peripheral blood cultures and central venous catheter cultures negative for infections
• No microbiological documentation of a bacterial infection (e.g., abscess at catheter site)
• No invasive fungal infection
• No probable noninfectious cause of fever

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• Karnofsky 40-100% OR
• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No prior anaphylactic reaction to amphotericin B
• No psychological, familial, sociological, or geographical conditions that would prevent compliance
• Not pregnant or nursing
• Normal chest X-ray or normal high resolution CT scan of the lungs

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent active systemic antifungal agents or antifungal prophylaxis (e.g., azoles or polyenes)
• No prior IV amphotericin B during same neutropenic episode
• No change in antibacterial regimen within 48 hours prior to study

Belgium
      A.Z. St. Jan, Brugge,  8000,  Belgium
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
Czech Republic
      University Hospital - Olomouc, Olomouc,  775 20,  Czech Republic
France
      Centre Hospitalier Universitaire Henri Mondor, Creteil,  94010,  France
      CHU de Caen, Caen,  14033,  France
      Hopital Saint-Louis, Paris,  75475,  France
Germany
      Universitaetsklinikum Charite, Berlin,  D-10117,  Germany
      Virchow Klinikum Humboldt Universitaet Berlin, Berlin,  D-13353,  Germany
Greece
      Athens University-Laikon General Hospital, Athens,  11527,  Greece
      Hippokration Hospital, THESSALONIKI,  54642,  Greece
Hungary
      Szent Laszlo Korhaz, Budapest,  1097,  Hungary
Israel
      Hadassah University Hospital, Jerusalem,  91120,  Israel
Italy
      Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova),  16132,  Italy
Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Portugal
      Hospital De Santo Antonio Dos Capuchos, Lisbon (Lisboa),  1100,  Portugal
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  812 50,  Slovakia
Spain
      Hospital Central de Asturias, Oviedo,  33006,  Spain
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain
Sweden
      Huddinge University Hospital, Stockholm,  SE-141 86,  Sweden
Turkey
      Section of Infectious Diseases, Ankara,  06100,  Turkey
United Arab Emirates
      Tawam Hospital, Abu Dhabi,  United Arab Emirates

Study chairs or principal investigators

P. Ljungman, MD,  Study Chair,  Huddinge University Hospital   

Study ID Numbers:  CDR0000067130; EORTC-19951
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003938
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08