Trial Outcomes & Findings for Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation (NCT NCT01371656)

Last Updated: 2020-12-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

624 participants

Primary outcome timeframe

Up to 60 days after enrollment or receiving levofloxacin

Results posted on

2020-12-07

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Levofloxacin) 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	Arm II (Standard of Care) Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Study STARTED	314	310
Overall Study COMPLETED	250	296
Overall Study NOT COMPLETED	64	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Levofloxacin) 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	Arm II (Standard of Care) Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Overall Study Death	7	4
Overall Study Physician Decision	46	7
Overall Study Withdrawal by Subject	7	0
Overall Study Ineligible	4	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Levofloxacin) n=314 Participants 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	Arm II (Standard of Care) n=310 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.	Total n=624 Participants Total of all reporting groups
Age, Categorical <=18 years	275 Participants n=5 Participants	284 Participants n=7 Participants	559 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	39 Participants n=5 Participants	26 Participants n=7 Participants	65 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	9.44 Years STANDARD_DEVIATION 6.18 • n=5 Participants	9.18 Years STANDARD_DEVIATION 5.89 • n=7 Participants	9.31 Years STANDARD_DEVIATION 6.03 • n=5 Participants
Sex: Female, Male Female	120 Participants n=5 Participants	127 Participants n=7 Participants	247 Participants n=5 Participants
Sex: Female, Male Male	194 Participants n=5 Participants	183 Participants n=7 Participants	377 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	89 Participants n=5 Participants	56 Participants n=7 Participants	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	208 Participants n=5 Participants	246 Participants n=7 Participants	454 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	8 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	22 Participants n=5 Participants	17 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	35 Participants n=5 Participants	45 Participants n=7 Participants	80 Participants n=5 Participants
Race (NIH/OMB) White	217 Participants n=5 Participants	216 Participants n=7 Participants	433 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	40 Participants n=5 Participants	32 Participants n=7 Participants	72 Participants n=5 Participants
Region of Enrollment United States	287 Participants n=5 Participants	272 Participants n=7 Participants	559 Participants n=5 Participants
Region of Enrollment Canada	26 Participants n=5 Participants	36 Participants n=7 Participants	62 Participants n=5 Participants
Region of Enrollment India	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Mexico	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Ireland	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 60 days after enrollment or receiving levofloxacin

Population: All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.

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.

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=306 Participants 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	Arm II (Standard of Care) n=307 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients Having Bacteremia Incidence Between Levofloxacin vs. No Prophylaxis Arms Evaluable AL patients	21.9 Percentage of patients	43.4 Percentage of patients
Comparison of the Percentage of Patients Having Bacteremia Incidence Between Levofloxacin vs. No Prophylaxis Arms Evaluable HSCT patients	11 Percentage of patients	17.3 Percentage of patients

SECONDARY outcome

Timeframe: Up to 60 days after enrollment or receiving levofloxacin

Population: All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.

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

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=306 Participants 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	Arm II (Standard of Care) n=307 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms Empiric antibiotics for fever and neutropenia	68.6 Percentage of patients	85.7 Percentage of patients
Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms Gram positive agents	58.8 Percentage of patients	65.8 Percentage of patients
Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms Aminoglycosides	22.9 Percentage of patients	35.5 Percentage of patients
Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms Third or fourth generation cephalosporins	46.1 Percentage of patients	59.9 Percentage of patients

SECONDARY outcome

Timeframe: Up to 60 days after enrollment or receiving levofloxacin

Population: All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.

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.

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=306 Participants 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	Arm II (Standard of Care) n=307 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients Having Incidence of Fever and Febrile Neutropenia Between Arms	71.2 Percentage of patients	82.1 Percentage of patients

SECONDARY outcome

Timeframe: Up to 60 days after enrollment or receiving levofloxacin

Population: All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.

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

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=306 Participants 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	Arm II (Standard of Care) n=307 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients Having Severe Infection Between Arms	3.6 Percentage of patients	5.9 Percentage of patients

SECONDARY outcome

Timeframe: Up to 60 days after enrollment or receiving levofloxacin

Population: Evaluable patients combined from both AL and HSCT cohorts were reported. Ineligible and withdrew of Consent prior to Tx were excluded.

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=306 Participants 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	Arm II (Standard of Care) n=307 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients That Died Due to Bacterial Infection Between Arms	0 Percentage of patients	0 Percentage of patients

SECONDARY outcome

Timeframe: Enrollment, 2 months and 12 months post infection observation period

Population: 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.

Musculoskeletal conditions included at least one occurrence of arthralgia, arthritis, gait abnormality or tendinopathy.

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=303 Participants 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	Arm II (Standard of Care) n=300 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms Evaluable AL and HSCT Patients at Baseline	5.9 Percentage of patients	10 Percentage of patients
Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms Evaluable AL and HSCT Patients at 2 Months	11.4 Percentage of patients	16.3 Percentage of patients
Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms Evaluable AL and HSCT Patients at 12 Months	10.1 Percentage of patients	14.4 Percentage of patients

SECONDARY outcome

Timeframe: Up to 60 days after enrollment or receiving levofloxacin

Population: All evaluable, and centrally reviewed AL and HSCT patients are reported. Ineligible patients and patients who withdrew of consent prior to treatment were excluded.

Clostridium Difficile Associated Disease (CDAD) is defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher.

Outcome measures

Outcome measures
Measure	Arm I (Levofloxacin) n=306 Participants 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	Arm II (Standard of Care) n=307 Participants Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Comparison of the Percentage of Patients Having Incidence of CDAD Between Arms	2.3 Percentage of patients	5.2 Percentage of patients

Adverse Events

Arm I (Levofloxacin)

Serious events: 4 serious events

Other events: 36 other events

Deaths: 69 deaths

Arm II (Standard of Care)

Serious events: 3 serious events

Other events: 37 other events

Deaths: 67 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Levofloxacin) n=306 participants at risk 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	Arm II (Standard of Care) n=307 participants at risk Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Renal and urinary disorders Acute kidney injury	0.33% 1/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.00% 0/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Vascular disorders Capillary leak syndrome	0.33% 1/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.00% 0/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
General disorders Death NOS	0.33% 1/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.33% 1/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Cardiac disorders Heart failure	0.00% 0/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.33% 1/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Infections and infestations Infections and infestations - Other, specify	0.65% 2/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.00% 0/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Infections and infestations Lung infection	0.00% 0/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.33% 1/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
General disorders Multi-organ failure	0.98% 3/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.00% 0/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.33% 1/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.00% 0/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.65% 2/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.33% 1/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events
Infections and infestations Sepsis	0.33% 1/306 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events	0.00% 0/307 • Up to 60 days after enrollment or receiving of levofloxacin Routine reporting includes all toxicities reported via AdEERs and all grade 4 \& higher non-hematologic Adverse Events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 352-273-0567

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
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