Clinical trial NCT00062231: Moxifloxacin Compared With Ciprofloxacin/Amoxicillin in Treating Fever and Neutropenia in Patients With Cancer
Official title: Oral Empirical Therapy of Fever in Low-Risk Neutropenic Cancer Patients: A Prospective, Double-Blind, Randomized, Multicenter Trial Comparing Monotherapy (Single Daily Dose Moxifloxacin) With Combination Therapy (Ciprofloxacin Plus Amoxicillin/Clavulanic Acid)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chronic Myeloproliferative Disorders
Fever, Sweats, and Hot Flashes
Infection
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Neutropenia
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: infection
neutropenia
fever, sweats, and hot flashes
unspecified adult solid tumor, protocol specific
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
monoclonal gammopathy of undetermined significance
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
stage 0 chronic lymphocytic leukemia
Waldenstrom macroglobulinemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
adult acute myeloid leukemia in remission
polycythemia vera
primary myelofibrosis
essential thrombocythemia
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
stage I adult diffuse large cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Burkitt lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
chronic myelomonocytic leukemia
T-cell large granular lymphocyte leukemia
acute undifferentiated leukemia
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult T-cell leukemia/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
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
prolymphocytic leukemia
primary systemic amyloidosis
intraocular lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
recurrent mantle cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent mycosis fungoides/Sezary syndrome
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
chronic eosinophilic leukemia
chronic neutrophilic leukemia
recurrent adult acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
contiguous stage II small lymphocytic lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic 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
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-06-06
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Antibiotics such as amoxicillin, ciprofloxacin, and moxifloxacin may be effective in preventing or controlling fever and neutropenia in patients with cancer. It is not yet known whether moxifloxacin alone is more effective than amoxicillin combined with ciprofloxacin in treating neutropenia and fever.

PURPOSE: This randomized clinical trial is studying how well moxifloxacin works and compares it to ciprofloxacin together with amoxicillin in treating neutropenia and fever in patients with cancer.

Detailed description: OBJECTIVES:

* Compare the rates of successful response to moxifloxacin vs ciprofloxacin in combination with amoxicillin-clavulanate potassium in low-risk febrile neutropenic patients with cancer.
* Compare the time to discharge, time to discontinuation of any antimicrobial therapy, and time to defervescence of patients treated with these regimens.
* Compare 28-day survival of patients treated with these regimens.
* Determine the proportion of these patients who are eligible for oral therapy and a therapeutic management including intention of early discharge.
* Determine the medical and nonmedical reasons for continued in-hospital observation and care or for readmission of these patients.
* Determine the accuracy of the physician's estimate of further neutropenia duration and evaluate its predictive value in these patients.
* Validate the Multinational Association for Supportive Care in Cancer low-risk prediction rule to predict the absence of serious medical complications in the setting of oral therapy in in- and outpatients.

OUTLINE: This is a double-blind, randomized, multicenter study. Patients are stratified according to institution, underlying disease (hematologic malignancy vs other), pretreatment with no more than a single dose (yes vs no), and outpatient status at fever onset (yes vs no). Patients are randomized into 1 of 2 treatment arms.

* Arm I: Patients receive oral moxifloxacin once daily. Patients also receive oral ciprofloxacin placebo and oral amoxicillin-clavulanate potassium placebo twice daily.
* Arm II: Patients receive oral ciprofloxacin and oral amoxicillin-clavulanate potassium twice daily. Patients also receive oral moxifloxacin placebo once daily.

Patients with fever classified as not related to infection (i.e., doubtful) stop antibiotic therapy on day 3. All other patients receive antibiotics until complete resolution of infection, or until failure is determined or anticipated, for up to 28 days.

Patients are followed at 7-10 days.

PROJECTED ACCRUAL: A total of 530 patients (265 patients per treatment arm) will be accrued for this study within approximately 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of cancer with developing febrile neutropenia

  * Neutropenia defined as an absolute granulocyte count of less than 1,000/mm\^3, expected to fall to less than 500/mm\^3 within 24 hours, secondary to administration of chemotherapy and/or radiotherapy within the past 30 days
  * Fever defined as an oral temperature greater than 38.5ºC once, or 38°C or greater on 2 or more occasions at least 1 hour apart during a 12-hour period, and suspected to be due to infection
* Expected low risk of serious medical complications as predicted by a Multinational Association for Supportive Care in Cancer risk-index score of greater than 20
* No obvious signs of exit-site or tunnel intravascular catheter infection
* No known or suspected CNS infection
* No known or highly suspected bacterial, viral, or fungal infection

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Not specified

Life expectancy

* No high probability of death within 48 hours before study enrollment (i.e., patients who are moribund or comatose for any reason with little hope of recovery OR patients in danger of, or in hepatic stupor or coma)

Hematopoietic

* See Disease Characteristics
* No signs or symptoms of uncontrolled bleeding

Hepatic

* Bilirubin no greater than 3 times upper limit of normal (ULN)
* Alkaline phosphatase no greater than 3 times ULN
* AST and ALT no greater than 5 times ULN
* No severe hepatic dysfunction

Renal

* Creatinine no greater than 3.4 mg/dL
* Creatinine clearance at least 25 mL/min
* No renal failure requiring hemodialysis or peritoneal dialysis

Cardiovascular

* No prior symptomatic arrhythmias
* No clinically relevant bradycardia
* No QTc interval prolongation
* No uncorrected hypokalemia
* No signs or symptoms of hypotension (systolic less than 90 mm Hg)

Pulmonary

* No signs or symptoms of respiratory insufficiency

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* Able to swallow oral medication
* No contraindication for oral drug intake
* No condition likely to severely impair drug absorption
* No prior immediate or accelerated reaction to penicillin, cephalosporin, or fluoroquinolone antibiotics
* No known allergy or hypersensitivity to any antibiotics in this study or other quinolones
* No signs or symptoms of severe dehydration
* No signs or symptoms of shock
* No other signs or symptoms at presentation that would necessitate IV supportive therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics

Surgery

* Not specified

Other

* More than 4 days since prior antibacterial agents except for the following:

  * A single (oral or parenteral therapeutic) dose after initial diagnosic work-up and within the last 8 hours
  * Low-dose cotrimoxazole (i.e., no more than 480 mg daily or 960 mg 3 times per week) prophylaxis of Pneumocystis carinii pneumonia
* More than 30 days since prior investigational drugs
* No prior randomization in this study
* No other concurrent antimicrobial agents
* No class IA or class III antiarrhythmic drugs or other concurrent drugs that prolong the QTc interval

Primary outcomes:
measure: Response as measured by International Antimicrobial Therapy Group (IATG) specific criteria at the completion of allocated treatment
Secondary outcomes:
measure: Rate of complication as measured by Multinational Association for Supportive Care in Cancer (MASCC) criteria at the end of febrile neutropenic episode
measure: Time to discharge as measured by Logrank continuously until the end of febrile neutropenic episode
measure: Time to defervescence as measured by Logrank continuously until the end of febrile neutropenic episode
measure: Survival status as measured by Logrank at day 28
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Bordeaux
country: France
facility: Institut Bergonie
city: Paris
country: France
facility: Institut Curie Hopital
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Freiburg
country: Germany
facility: Klinikum der Albert - Ludwigs - Universitaet Freiburg
city: Heidelberg
country: Germany
facility: Ruprecht - Karls - Universitaet Heidelberg
city: Mannheim
country: Germany
facility: Klinikum der Stadt Mannheim
city: Rostock
country: Germany
facility: Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Genoa
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Udine
country: Italy
facility: Universita Degli Studi di Udine
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Bratislava
country: Slovakia
facility: St. Elizabeth Cancer Institute Hospital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Yverdon
country: Switzerland
facility: Hopital D'Yverdon
city: Ankara
country: Turkey
facility: Hacettepe University - Faculty of Medicine
city: Ankara
country: Turkey
facility: Ibn-i Sina Hospital
city: Istanbul
country: Turkey
facility: Marmara University Hospital
Study officials:
affiliation: University Hospital Freiburg
name: Winfried Kern, MD
role: STUDY_CHAIR
References:
citation: Kern WV, Marchetti O, Drgona L, Akan H, Aoun M, Akova M, de Bock R, Paesmans M, Viscoli C, Calandra T. Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, randomized, multicenter trial comparing single daily moxifloxacin with twice daily ciprofloxacin plus amoxicillin/clavulanic acid combination therapy--EORTC infectious diseases group trial XV. J Clin Oncol. 2013 Mar 20;31(9):1149-56. doi: 10.1200/JCO.2012.45.8109. Epub 2013 Jan 28.