Clinical trial NCT00003805: Prevention of Infection in Patients With Hematologic Cancer and Persistent Fever Caused by a Low White Blood Cell Count
Official title: Vancomycin Versus Placebo in Persistently Febrile Granulocytopenic Patients Given Piperacillin/Tazobactam
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Marrow Suppression
Fever, Sweats, and Hot Flashes
Infection
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Unspecified Adult Solid Tumor, Protocol Specific
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
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
Burkitt lymphoma
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
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
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
fever, sweats, and hot flashes
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 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
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
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
infection
bone marrow suppression
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
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: 2004-07-16
Enrollment: 859
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Antibiotic therapy may prevent the development of infection in patients with hematologic cancer and the persistent fever caused by a low white blood cell count. It is not yet known which regimen of antibiotics is most effective in preventing infection in these patients.

PURPOSE: Randomized phase III trial to study the effectiveness of piperacillin-tazobactam with or without vancomycin in reducing fever in patients who have leukemia, lymphoma, or Hodgkin's disease.

Detailed description: OBJECTIVES: I. Compare the efficacy of piperacillin and tazobactam with or without vancomycin in reducing fever in patients with hematological malignancies and persistent febrile granulocytopenia.

OUTLINE: This is a randomized, double blind, multicenter study. Patients receive piperacillin/tazobactam IV over 20-30 minutes every 6 hours. Patients who become afebrile within 48-60 hours after beginning treatment continue to receive piperacillin/tazobactam alone. These afebrile patients continue treatment for a minimum of 7 days, of which 4 must be consecutive without fever. Patients who are still febrile after the initial 48-60 hours are randomized to continue on piperacillin/tazobactam alone or with vancomycin. Vancomycin IV is administered over at least 1 hour twice daily. Treatment continues for a maximum of 28 days in the absence of persistent fever. Patients are followed at 7-10 days after completion of therapy.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Leukemia, lymphoma, or Hodgkin's disease OR Stem cell transplantation or bone marrow transplantation (allogenic or autologous) for a neoplastic disease Absolute granulocyte count no greater than 1,000/mm3 anticipated to fall below 500/mm3 within 24-48 hours, and expected to last for longer than 7 days from onset of fever Fever (i.e., oral or axillary temperature at least 38.5 degrees C or 101.3 degrees F once, or at least 38 degrees C or 100.4 degrees F on two or more occasions separated at least by 1 hour during a 12 hour period) Presumed infection

PATIENT CHARACTERISTICS: Age: 2 and over Performance status: Not moribund or comatose for any reason with little hope of recovery Life expectancy: At least 48 hours Hematopoietic: See Disease Characteristics Hepatic: No hepatic stupor or coma Renal: Adults: No renal failure requiring hemodialysis or peritoneal dialysis OR Creatinine no greater than 2.25 mg/dL OR Creatinine clearance at least 40 mL/min Children: No renal impairment (i.e., creatinine greater than upper limit of normal) Pulmonary: No lung infiltrate Other: No known allergy to piperacillin, tazobactam, or vancomycin No history of immediate or accelerated reaction to beta-lactam antibiotics No prior inclusion in this study No catheter related infection No known HIV infection Not pregnant or nursing

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 4 days since prior intravenous antibacterial agents Oral antibiotics for prophylaxis of bacterial infection allowed At least 30 days since prior treatment with any other investigational antibiotic No other concurrent antibiotics except trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Antwerp
country: Belgium
facility: Algemeen Ziekenhuis Middelheim
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Brussels (Bruxelles)
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Center - General Division
state: Ontario
city: Brno
country: Czech Republic
facility: Masaryk University Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Besancon
country: France
facility: CHR de Besancon - Hopital Saint-Jacques
city: Ulm
country: Germany
facility: Klinikum der Universitaet Ulm
city: Athens
country: Greece
facility: Hellenic Institute for Cancer-Saint Savas Hospital
city: Athens
country: Greece
facility: Athens University-Laikon General Hospital
city: Piraeus
country: Greece
facility: Metaxa's Memorial Cancer Hospital
city: Rio Patras
country: Greece
facility: University of Patras Medical School
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Bratislava
country: Slovakia
facility: St. Elizabeth Cancer Institute Hospital
city: Bellinzona
country: Switzerland
facility: Ospedale San Giovanni
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zurich
country: Switzerland
facility: Universitaetsspital
city: Ankara
country: Turkey
facility: Ibn-i Sina Hospital, Ankara Univeristy
city: Ankara
country: Turkey
facility: Section of Infectious Diseases
city: Istanbul
country: Turkey
facility: Marmara University Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: England
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Michel P. Glauser, MD
role: STUDY_CHAIR
References: