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.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Multiple Myeloma	Drug: piperacillin  Drug: tazobactam  Drug: vancomycin	Phase III

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  2 Years and above

Criteria

PROTOCOL ENTRY 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

--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

--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

Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Cliniques Universitaires Saint-Luc, Brussels (Bruxelles),  1200,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels (Bruxelles),  1000,  Belgium
Canada, Ontario
      Kingston General Hospital, Kingston,  Ontario,  K7L 2V7,  Canada
      Ottawa Regional Cancer Center - General Division, Ottawa,  Ontario,  K1H 8L6,  Canada
Czech Republic
      Masaryk University Hospital, Brno,  639 00,  Czech Republic
Finland
      Turku University Central Hospital, Turku,  FIN-2-0521,  Finland
France
      CHR de Besancon - Hopital Saint-Jacques, Besancon,  25030,  France
Germany
      Klinikum der Universitaet Ulm, Ulm,  D-89081,  Germany
Greece
      Athens University-Laikon General Hospital, Athens,  11527,  Greece
      Hellenic Institute for Cancer-Saint Savas Hospital, Athens,  11522,  Greece
      Metaxa's Memorial Cancer Hospital, Piraeus,  18537,  Greece
      University of Patras Medical School, Rio Patras,  GR-26500,  Greece
Israel
      Chaim Sheba Medical Center, RAMAT-GAN,  52621,  Israel
      Hadassah University Hospital, Jerusalem,  91120,  Israel
      Wolfson Medical Center, Holon,  58100,  Israel
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia
      St. Elizabeth Cancer Institute Hospital, Bratislava,  SK-81250,  Slovakia
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
      Ospedale San Giovanni, Bellinzona,  CH-6500,  Switzerland
      Universitaetsspital, Zurich,  CH-8091,  Switzerland
Turkey
      Ibn-i Sina Hospital, Ankara Univeristy, Ankara,  06100,  Turkey
      Marmara University Hospital, Istanbul,  81190,  Turkey
      Section of Infectious Diseases, Ankara,  06100,  Turkey
United Kingdom, England
      Royal Marsden Hospital, Sutton,  England,  SM2 5PT,  United Kingdom

Study chairs or principal investigators

Michel P. Glauser,  Study Chair,  EORTC International Antimicrobial Therapy Group   

Study ID Numbers:  CDR0000066949; EORTC-46971
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003805
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08