Clinical trial NCT00003938: Liposomal Amphotericin B in Treating Granulocytopenia and Persistent Unexplained Fever in Cancer Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Keywords: 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
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
disseminated neuroblastoma
recurrent neuroblastoma
recurrent Wilms tumor and other childhood kidney tumors
stage 0 chronic lymphocytic leukemia
Waldenstrom macroglobulinemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
small intestine lymphoma
stage III malignant testicular germ cell tumor
recurrent malignant testicular germ cell tumor
unspecified childhood solid tumor, protocol specific
unspecified adult solid tumor, protocol specific
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
polycythemia vera
primary myelofibrosis
essential thrombocythemia
fever, sweats, and hot flashes
childhood acute promyelocytic leukemia (M3)
testicular embryonal carcinoma
testicular choriocarcinoma
testicular teratoma
testicular yolk sac tumor
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and teratoma with seminoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular embryonal carcinoma and seminoma
testicular yolk sac tumor and teratoma
testicular yolk sac tumor and teratoma with seminoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and seminoma
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
stage II childhood Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I adult Burkitt lymphoma
recurrent ovarian germ cell tumor
chronic myelomonocytic leukemia
T-cell large granular lymphocyte leukemia
ovarian yolk sac tumor
ovarian embryonal carcinoma
ovarian polyembryoma
ovarian choriocarcinoma
ovarian immature teratoma
ovarian mature teratoma
ovarian monodermal and highly specialized teratoma
ovarian mixed germ cell tumor
acute undifferentiated leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
de novo myelodysplastic syndromes
high risk metastatic gestational trophoblastic tumor
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
primary central nervous system non-Hodgkin lymphoma
neutropenia
infection
previously untreated childhood rhabdomyosarcoma
prolymphocytic leukemia
primary systemic amyloidosis
intraocular lymphoma
stage I childhood small noncleaved cell lymphoma
stage I childhood large cell lymphoma
stage II childhood small noncleaved cell lymphoma
stage II childhood large cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood small noncleaved cell lymphoma
stage IV childhood large cell lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
stage I mantle cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
previously treated childhood rhabdomyosarcoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
childhood chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic neutrophilic leukemia
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage I marginal zone lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
childhood myelodysplastic syndromes
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 115
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: A.Z. St. Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Mont-Godinne Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: Olomouc
country: Czech Republic
facility: University Hospital - Olomouc
city: Caen
country: France
facility: CHU de Caen
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Paris
country: France
facility: Hopital Saint-Louis
city: Berlin
country: Germany
facility: Universitaetsklinikum Charite
city: Berlin
country: Germany
facility: Virchow Klinikum Humboldt Universitaet Berlin
city: Athens
country: Greece
facility: Athens University-Laikon General Hospital
city: Thessaloniki
country: Greece
facility: Hippokration Hospital
city: Budapest
country: Hungary
facility: Szent Laszlo Korhaz
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Genoa (Genova)
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Lisbon (Lisboa)
country: Portugal
facility: Hospital De Santo Antonio Dos Capuchos
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz I Sant Pau
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Stockholm
country: Sweden
facility: Huddinge University Hospital
city: Ankara
country: Turkey
facility: Section of Infectious Diseases
city: Abu Dhabi
country: United Arab Emirates
facility: Tawam Hospital
Study officials:
affiliation: Karolinska Institutet
name: P. Ljungman, MD
role: STUDY_CHAIR
References: