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Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

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ClinicalTrials.gov Identifier: NCT01371656
Recruitment Status : Completed
First Posted : June 13, 2011
Results First Posted : June 25, 2018
Last Update Posted : July 24, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single;   Primary Purpose: Supportive Care
Conditions Acute Leukemias of Ambiguous Lineage
Bacterial Infection
Diarrhea
Fungal Infection
Musculoskeletal Complications
Neutropenia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Intervention Drug: levofloxacin
Enrollment 624

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Period Title: Overall Study
Started 314 310
Completed 250 296
Not Completed 64 14
Reason Not Completed
Death             7             4
Physician Decision             46             7
Withdrawal by Subject             7             0
Ineligible             4             3
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care) Total
Hide Arm/Group Description

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I. Total of all reporting groups
Overall Number of Baseline Participants 314 310 624
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 310 participants 624 participants
<=18 years
275
  87.6%
284
  91.6%
559
  89.6%
Between 18 and 65 years
39
  12.4%
26
   8.4%
65
  10.4%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Standard Deviation)
Unit of measure:  Years
Number Analyzed 314 participants 310 participants 624 participants
9.44  (6.18) 9.18  (5.89) 9.31  (6.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 310 participants 624 participants
Female
120
  38.2%
127
  41.0%
247
  39.6%
Male
194
  61.8%
183
  59.0%
377
  60.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 310 participants 624 participants
Hispanic or Latino
89
  28.3%
56
  18.1%
145
  23.2%
Not Hispanic or Latino
208
  66.2%
246
  79.4%
454
  72.8%
Unknown or Not Reported
17
   5.4%
8
   2.6%
25
   4.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 310 participants 624 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
22
   7.0%
17
   5.5%
39
   6.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
35
  11.1%
45
  14.5%
80
  12.8%
White
217
  69.1%
216
  69.7%
433
  69.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
40
  12.7%
32
  10.3%
72
  11.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 310 participants 624 participants
United States
287
  91.4%
272
  87.7%
559
  89.6%
Canada
26
   8.3%
36
  11.6%
62
   9.9%
India
1
   0.3%
0
   0.0%
1
   0.2%
Mexico
0
   0.0%
1
   0.3%
1
   0.2%
Ireland
0
   0.0%
1
   0.3%
1
   0.2%
1.Primary Outcome
Title Comparison of the Percentage of Patients Having Bacteremia Incidence Between Levofloxacin vs. No Prophylaxis Arms
Hide Description A bacteremia incidence is defined as an occurrence of at least 1 episode of true (centrally reviewed) bacteremia among Acute Leukemia (AL) and Hematopoietic stem cell transplantation (HSCT) patients.
Time Frame Up to 60 days after enrollment or receiving levofloxacin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 306 307
Measure Type: Number
Unit of Measure: Percentage of patients
Evaluable AL patients Number Analyzed 96 participants 99 participants
21.9 43.4
Evaluable HSCT patients Number Analyzed 210 participants 208 participants
11 17.3
2.Secondary Outcome
Title Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms
Hide Description Exposure to antibiotics was considered during the infection observation period(s) was defined a priori as follows: Gram positive agents = vancomycin, linezolid, daptomycin or quinupristin/dalfopristin; Aminoglycosides = amikacin, gentamicin or tobramycin; Third or fourth generation cephalosporins = cefepime, ceftazidime, ceftriaxone or cefotaxime; Empiric antibiotics for fever and neutropenia = imipenem, meropenem, cefepime, ceftazidime or piperacillin/tazobactam
Time Frame Up to 60 days after enrollment or receiving levofloxacin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 306 307
Measure Type: Number
Unit of Measure: Percentage of patients
Gram positive agents 58.8 65.8
Aminoglycosides 22.9 35.5
Third or fourth generation cephalosporins 46.1 59.9
Empiric antibiotics for fever and neutropenia 68.6 85.7
3.Secondary Outcome
Title Comparison of the Percentage of Patients Having Incidence of Fever and Febrile Neutropenia Between Arms
Hide Description Fever and febrile neutropenia defined as Absolute Neutrophil Count (ANC) < 1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >= 38 degrees C (100.4 degrees F) for more than one hour.
Time Frame Up to 60 days after enrollment or receiving levofloxacin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 306 307
Measure Type: Number
Unit of Measure: Percentage of patients
71.2 82.1
4.Secondary Outcome
Title Comparison of the Percentage of Patients Having Severe Infection Between Arms
Hide Description Severe infection defined as any grade 4 or 5 CTCAE catheter-related infection, enterocolitis, lung infection, sepsis, small intestine infection and other infections or infestations
Time Frame Up to 60 days after enrollment or receiving levofloxacin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 306 307
Measure Type: Number
Unit of Measure: Percentage of patients
3.6 5.9
5.Secondary Outcome
Title Comparison of the Percentage of Patients That Died Due to Bacterial Infection Between Arms
Hide Description [Not Specified]
Time Frame Up to 60 days after enrollment or receiving levofloxacin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Evaluable patients combined from both AL and HSCT cohorts were reported. Ineligible and withdrew of Consent prior to Tx were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 306 307
Measure Type: Number
Unit of Measure: Percentage of patients
0 0
6.Secondary Outcome
Title Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms
Hide Description Musculoskeletal conditions included at least one occurrence of arthralgia, arthritis, gait abnormality or tendinopathy.
Time Frame Enrollment, 2 months and 12 months post infection observation period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Evaluable patients who submitted musculoskeletal Case Record Form (CRF) combined from both Acute Leukemia (AL) and Hematopoietic stem cell transplantation (HSCT) cohorts at enrollment. Ineligible and withdrew of Consent prior to treatment were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 303 300
Measure Type: Number
Unit of Measure: Percentage of patients
Evaluable AL and HSCT Patients at Baseline Number Analyzed 303 participants 300 participants
5.9 10
Evaluable AL and HSCT Patients at 2 Months Number Analyzed 201 participants 240 participants
11.4 16.3
Evaluable AL and HSCT Patients at 12 Months Number Analyzed 129 participants 146 participants
10.1 14.4
7.Secondary Outcome
Title Comparison of the Percentage of Patients Having Incidence of CDAD Between Arms
Hide Description Clostridium Difficile Associated Disease (CDAD) is defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher.
Time Frame Up to 60 days after enrollment or receiving levofloxacin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description:

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Number of Participants Analyzed 306 307
Measure Type: Number
Unit of Measure: Percentage of patients
2.3 5.2
Time Frame Up to 60 days after enrollment or receiving of levofloxacin
Adverse Event Reporting Description Routine reporting includes all toxicities reported via AdEERs and all grade 4 & higher non-hematologic Adverse Events
 
Arm/Group Title Arm I (Levofloxacin) Arm II (Standard of Care)
Hide Arm/Group Description

Patients receive levofloxacin PO or IV over 60-90 minutes once or twice daily beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.

levofloxacin: Given PO or IV

Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
All-Cause Mortality
Arm I (Levofloxacin) Arm II (Standard of Care)
Affected / at Risk (%) Affected / at Risk (%)
Total   69/306 (22.55%)   67/307 (21.82%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Levofloxacin) Arm II (Standard of Care)
Affected / at Risk (%) Affected / at Risk (%)
Total   4/306 (1.31%)   3/307 (0.98%) 
Cardiac disorders     
Heart failure  1  0/306 (0.00%)  1/307 (0.33%) 
General disorders     
Death NOS  1  1/306 (0.33%)  1/307 (0.33%) 
Multi-organ failure  1  3/306 (0.98%)  0/307 (0.00%) 
Infections and infestations     
Infections and infestations - Other, specify  1  2/306 (0.65%)  0/307 (0.00%) 
Lung infection  1  0/306 (0.00%)  1/307 (0.33%) 
Sepsis  1  1/306 (0.33%)  0/307 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/306 (0.33%)  0/307 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary edema  1  1/306 (0.33%)  0/307 (0.00%) 
Respiratory failure  1  2/306 (0.65%)  1/307 (0.33%) 
Vascular disorders     
Capillary leak syndrome  1  1/306 (0.33%)  0/307 (0.00%) 
1
Term from vocabulary, CTCAE v4.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (Levofloxacin) Arm II (Standard of Care)
Affected / at Risk (%) Affected / at Risk (%)
Total   36/306 (11.76%)   37/307 (12.05%) 
Blood and lymphatic system disorders     
Disseminated intravascular coagulation  1  0/306 (0.00%)  1/307 (0.33%) 
Cardiac disorders     
Asystole  1  0/306 (0.00%)  1/307 (0.33%) 
Cardiac arrest  1  0/306 (0.00%)  2/307 (0.65%) 
Left ventricular systolic dysfunction  1  0/306 (0.00%)  1/307 (0.33%) 
Pericardial effusion  1  1/306 (0.33%)  0/307 (0.00%) 
Sinus bradycardia  1  0/306 (0.00%)  1/307 (0.33%) 
Ventricular fibrillation  1  1/306 (0.33%)  1/307 (0.33%) 
Gastrointestinal disorders     
Diarrhea  1  1/306 (0.33%)  0/307 (0.00%) 
Ileal hemorrhage  1  0/306 (0.00%)  1/307 (0.33%) 
Mucositis oral  1  2/306 (0.65%)  4/307 (1.30%) 
General disorders     
Multi-organ failure  1  0/306 (0.00%)  1/307 (0.33%) 
Hepatobiliary disorders     
Hepatic failure  1  0/306 (0.00%)  1/307 (0.33%) 
Hepatobiliary disorders - Other, specify  1  2/306 (0.65%)  1/307 (0.33%) 
Portal hypertension  1  1/306 (0.33%)  0/307 (0.00%) 
Portal vein thrombosis  1  0/306 (0.00%)  1/307 (0.33%) 
Immune system disorders     
Anaphylaxis  1  1/306 (0.33%)  0/307 (0.00%) 
Infections and infestations     
Catheter related infection  1  0/306 (0.00%)  1/307 (0.33%) 
Enterocolitis infectious  1  0/306 (0.00%)  1/307 (0.33%) 
Infections and infestations - Other, specify  1  1/306 (0.33%)  4/307 (1.30%) 
Lung infection  1  0/306 (0.00%)  1/307 (0.33%) 
Sepsis  1  8/306 (2.61%)  11/307 (3.58%) 
Small intestine infection  1  0/306 (0.00%)  1/307 (0.33%) 
Investigations     
Alanine aminotransferase increased  1  3/306 (0.98%)  4/307 (1.30%) 
Aspartate aminotransferase increased  1  2/306 (0.65%)  2/307 (0.65%) 
Blood bilirubin increased  1  3/306 (0.98%)  2/307 (0.65%) 
Fibrinogen decreased  1  1/306 (0.33%)  0/307 (0.00%) 
GGT increased  1  2/306 (0.65%)  3/307 (0.98%) 
Neutrophil count decreased  1  0/306 (0.00%)  1/307 (0.33%) 
Platelet count decreased  1  0/306 (0.00%)  1/307 (0.33%) 
Metabolism and nutrition disorders     
Acidosis  1  0/306 (0.00%)  2/307 (0.65%) 
Alkalosis  1  0/306 (0.00%)  1/307 (0.33%) 
Hyperglycemia  1  4/306 (1.31%)  2/307 (0.65%) 
Hyperkalemia  1  0/306 (0.00%)  1/307 (0.33%) 
Hypernatremia  1  0/306 (0.00%)  1/307 (0.33%) 
Hypertriglyceridemia  1  2/306 (0.65%)  0/307 (0.00%) 
Hypoalbuminemia  1  0/306 (0.00%)  1/307 (0.33%) 
Hypocalcemia  1  1/306 (0.33%)  3/307 (0.98%) 
Hypokalemia  1  3/306 (0.98%)  5/307 (1.63%) 
Hypomagnesemia  1  0/306 (0.00%)  1/307 (0.33%) 
Hyponatremia  1  1/306 (0.33%)  2/307 (0.65%) 
Nervous system disorders     
Depressed level of consciousness  1  0/306 (0.00%)  1/307 (0.33%) 
Encephalopathy  1  0/306 (0.00%)  1/307 (0.33%) 
Intracranial hemorrhage  1  0/306 (0.00%)  1/307 (0.33%) 
Nervous system disorders - Other, specify  1  0/306 (0.00%)  1/307 (0.33%) 
Reversible posterior leukoencephalopathy syndrome  1  1/306 (0.33%)  0/307 (0.00%) 
Seizure  1  0/306 (0.00%)  1/307 (0.33%) 
Renal and urinary disorders     
Acute kidney injury  1  1/306 (0.33%)  1/307 (0.33%) 
Renal and urinary disorders - Other, specify  1  1/306 (0.33%)  1/307 (0.33%) 
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1  1/306 (0.33%)  2/307 (0.65%) 
Atelectasis  1  0/306 (0.00%)  1/307 (0.33%) 
Bronchopulmonary hemorrhage  1  1/306 (0.33%)  0/307 (0.00%) 
Dyspnea  1  1/306 (0.33%)  2/307 (0.65%) 
Hypoxia  1  0/306 (0.00%)  3/307 (0.98%) 
Pleural effusion  1  1/306 (0.33%)  0/307 (0.00%) 
Pulmonary edema  1  2/306 (0.65%)  1/307 (0.33%) 
Respiratory failure  1  2/306 (0.65%)  5/307 (1.63%) 
Respiratory, thoracic and mediastinal disorders - Other, specify  1  1/306 (0.33%)  2/307 (0.65%) 
Stridor  1  0/306 (0.00%)  1/307 (0.33%) 
Vascular disorders     
Capillary leak syndrome  1  1/306 (0.33%)  0/307 (0.00%) 
Hypotension  1  3/306 (0.98%)  4/307 (1.30%) 
1
Term from vocabulary, CTCAE v4.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 352-273-0567
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01371656     History of Changes
Other Study ID Numbers: ACCL0934
NCI-2011-02636 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000695661 ( Other Identifier: ClinicalTrials.gov )
ACCL0934 ( Other Identifier: Children's Oncology Group )
COG-ACCL0934 ( Other Identifier: DCP )
ACCL0934 ( Other Identifier: CTEP )
U10CA095861 ( U.S. NIH Grant/Contract )
First Submitted: June 4, 2011
First Posted: June 13, 2011
Results First Submitted: May 25, 2018
Results First Posted: June 25, 2018
Last Update Posted: July 24, 2018