Liposomal Amphotericin B in Treating Granulocytopenia and Persistent Unexplained Fever in Cancer Patients

• ClinicalTrials.gov Identifier: NCT00003938
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: September 24, 2012
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Cancer	Drug: liposomal amphotericin B	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 115 participants
• Allocation: Randomized
• Primary Purpose: Supportive Care
• Official Title: A Strategic Study to Determine the Optimal Moment to Initiate Systemic Antifungal Therapy With Ambisome in Granulocytopenic Cancer Patients With Unexplained Fever Refractory to Empirical Antibacterials
• Study Start Date: June 1999
• Actual Primary Completion Date: May 2003

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Hide Study Locations

Locations

Belgium

A.Z. St. Jan

Brugge, Belgium, 8000

Institut Jules Bordet

Brussels, Belgium, 1000

Hopital Universitaire Erasme

Brussels, Belgium, 1070

U.Z. Gasthuisberg

Leuven, Belgium, B-3000

Clinique Universitaire De Mont-Godinne

Mont-Godinne Yvoir, Belgium, 5530

Czech Republic

University Hospital - Olomouc

Olomouc, Czech Republic, 775 20

France

CHU de Caen

Caen, France, 14033

Centre Hospitalier Universitaire Henri Mondor

Creteil, France, 94010

Hopital Saint-Louis

Paris, France, 75475

Germany

Universitaetsklinikum Charite

Berlin, Germany, D-10117

Virchow Klinikum Humboldt Universitaet Berlin

Berlin, Germany, D-13353

Greece

Athens University-Laikon General Hospital

Athens, Greece, 11527

Hippokration Hospital

Thessaloniki, Greece, 54642

Hungary

Szent Laszlo Korhaz

Budapest, Hungary, 1097

Israel

Hadassah University Hospital

Jerusalem, Israel, 91120

Italy

Istituto Nazionale per la Ricerca sul Cancro

Genoa (Genova), Italy, 16132

Netherlands

University Medical Center Nijmegen

Nijmegen, Netherlands, NL-6500 HB

Portugal

Hospital De Santo Antonio Dos Capuchos

Lisbon (Lisboa), Portugal, 1100

Slovakia

National Cancer Institute - Bratislava

Bratislava, Slovakia, 812 50

Spain

Hospital de la Santa Cruz I Sant Pau

Barcelona, Spain, 08025

Hospital Central de Asturias

Oviedo, Spain, 33006

Sweden

Huddinge University Hospital

Stockholm, Sweden, SE-141 86

Turkey

Section of Infectious Diseases

Ankara, Turkey, 06100

United Arab Emirates

Tawam Hospital

Abu Dhabi, United Arab Emirates

Sponsors and Collaborators

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

• Study Chair: P. Ljungman, MD; Karolinska Institutet

More Information

• Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• ClinicalTrials.gov Identifier: NCT00003938 History of Changes
• Other Study ID Numbers: EORTC-19951; EORTC-19951
• First Posted: January 27, 2003
• Last Update Posted: September 24, 2012
• Last Verified: September 2012

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:

testicular teratoma; testicular embryonal carcinoma and teratoma; testicular embryonal carcinoma and teratoma with seminoma; testicular yolk sac tumor and teratoma; testicular yolk sac tumor and teratoma with seminoma; testicular choriocarcinoma and teratoma; ovarian immature teratoma; ovarian mature teratoma; ovarian monodermal and highly specialized teratoma; stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage IV breast cancer; stage IIIA breast cancer; monoclonal gammopathy of undetermined significance; stage IIIB breast cancer; recurrent childhood acute lymphoblastic leukemia; recurrent adult Hodgkin lymphoma; stage I cutaneous T-cell non-Hodgkin lymphoma; stage II cutaneous T-cell non-Hodgkin lymphoma; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; isolated plasmacytoma of bone; extramedullary plasmacytoma; refractory multiple myeloma; recurrent childhood rhabdomyosarcoma; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer

Additional relevant MeSH terms:

Anti-Bacterial Agents; Fever; Body Temperature Changes; Signs and Symptoms; Amphotericin B; Liposomal amphotericin B; Amebicides; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Antifungal Agents