Clinical trial NCT00445497: Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
Official title: A Prospective Randomised Phase III Trial of Early Hospital Discharge Versus Standard Inpatient Management of Cancer Patients With Low-Risk Febrile Neutropenia Receiving Oral Antibiotics. Oral Antibiotics for Neutropenic Sepsis Giving Early Hospital Discharge [ORANGE]
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Brain and Central Nervous System Tumors
Lymphoma
Neutropenia
Psychosocial Effects of Cancer and Its Treatment
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: psychosocial effects of cancer and its treatment
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
intraocular lymphoma
nodal marginal zone B-cell lymphoma
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent small lymphocytic lymphoma
small intestine lymphoma
splenic marginal zone lymphoma
stage III 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 Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult T-cell leukemia/lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III mycosis fungoides/Sezary syndrome
stage III small lymphocytic lymphoma
stage IV 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 Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult T-cell leukemia/lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV mycosis fungoides/Sezary syndrome
stage IV small lymphocytic lymphoma
Waldenström macroglobulinemia
unspecified adult solid tumor, protocol specific
neutropenia
stage I 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 Hodgkin lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage II adult Hodgkin lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
contiguous stage II adult Burkitt 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 immunoblastic large cell lymphoma
contiguous stage II adult lymphoblastic 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 mantle cell lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
noncontiguous 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 immunoblastic large cell lymphoma
noncontiguous 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 mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
recurrent adult T-cell leukemia/lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
adult grade III lymphomatoid granulomatosis
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-03-09
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Finishing an antibiotic regimen at home may be as effective as receiving it in the hospital. It is not yet known whether early hospital discharge is as effective as standard inpatient care in cancer patients receiving antibiotics for febrile neutropenia.

PURPOSE: This randomized phase III trial is studying early hospital discharge and comparing it with standard inpatient care in cancer patients receiving antibiotics for febrile neutropenia.

Detailed description: OBJECTIVES:

* Identify cancer patients who are low-risk inpatients and meet criteria for early discharge (i.e., symptomatic improvement and temperature ≤ 37.8°C) after receiving oral antibiotics for febrile neutropenia.

OUTLINE: This is a randomized, prospective, multicenter study. Patients are stratified by disease type (lymphoma vs solid tumor), duration of registration (\< 48 hours vs \> 48 hours), and participating center.

Patients receive oral amoxicillin-clavulanate potassium 3 times daily and oral ciprofloxacin twice daily on admission to the hospital. Treatment continues for 7 days in the absence of clinical deterioration or unacceptable toxicity. Patients are assessed as inpatients after ≥ 24 and up to 72 hours after the first antibiotic dose. Patients showing clear response (i.e., symptomatic improvement irrespective of neutrophil recovery, temperature ≤ 37.8 C for 24 hours) and who continue to meet study eligibility criteria are randomized to 1 of 2 arms.

* Arm I (early discharge): Patients are discharged home and instructed to remain in daily contact with hospital staff to report temperature and symptoms until completion of oral antibiotic regimen.
* Arm II (standard management): Patients continue their antibiotic course in hospital and are discharged according to local guidelines and the following additional criteria: subjective improvement, afebrile (≤ 37°C for 24 hours), and absolute neutrophil count ≥ 500/mm³ and rising.

Patients in both arms complete a daily diary documenting daily temperature readings, symptoms, and toxicities. Patients also complete a Health Questionnaire and a Cancer Worries Inventory Booklet at baseline, in the hospital immediately after randomization, and at completion of oral antibiotics or resolution of neutropenic febrile episode.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of solid tumor or lymphoma AND meets the following criteria:

  * Low-risk patient, defined as Multinational Association for Supportive Care in Cancer prognostic index score ≥ 21
  * Presents with neutropenic fever defined as follows:

    * Absolute neutrophil count ≤ 500/mm³ OR \< 1,000/mm³ but anticipated to fall to ≤ 500/mm³ within 24 hours of study entry
    * Temperature ≥ 38.5°C on a single measurement or ≥ 38.0°C on \> 1 occasion (one of which could be measured by the patient prior to admission) ≥ 1 hour apart
  * Undergoing concurrent cytotoxic chemotherapy for treatment of solid tumors or lymphoma
* No leukemia

PATIENT CHARACTERISTICS:

* Compliant and appropriate for early discharge
* Able to read a thermometer (patient or caregiver)
* Able to tolerate oral medication
* Must have a responsible adult caregiver if eligible for early discharge
* No known allergy to oral antibiotics or penicillin
* No requirement for IV fluid support
* No central venous catheter-associated infection or evidence of infection not amenable to treatment by study antibiotics
* No neutropenic fever at high risk of complications
* No associated comorbidity that requires hospitalization and management
* No known HIV positivity

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior participation in this study for neutropenic episode
* No prior bone marrow transplantation or peripheral blood stem cell transplantation
* No prior treatment for leukemia
* More than 72 hours since prior antibiotics, including prophylactic antibiotics

  * Prophylactic septrin (for pneumocystis), acyclovir, or antifungals are allowed
* No concurrent granulocyte colony-stimulating factor therapy

Primary outcomes:
measure: Total number of days of hospitalization (including unplanned readmission) (randomized patients)
measure: Incidence of serious adverse events (randomized and registered patients)
Secondary outcomes:
measure: Incidence of treatment failure as defined by the necessity for change in antibiotic therapy (randomized and registered patients)
measure: Incidence of unplanned readmissions (randomized patients)
measure: Patient acceptability of randomized discharge policy as measured by Health Questionnaire, Cancer Worries Inventory Booklet, and Patient Daily Diary (randomized patients)
measure: Toxicity attributed to oral antibiotic therapy as measured by NCI CTCAE v3.0 (randomized and registered patients)
measure: Health service costs (randomized patients)
Other outcomes:
Locations:
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: West Yorkshire
country: United Kingdom
facility: Airedale General Hospital
state: England
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
Study officials:
affiliation: Clatterbridge Centre for Oncology
name: Ernest Marshall, MD
role: STUDY_CHAIR
References: