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 26, 2018
Last Update Posted : December 7, 2020
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|Condition or disease||Intervention/treatment||Phase|
|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||Drug: levofloxacin||Phase 3|
I. To determine whether levofloxacin given prophylactically during periods of neutropenia to patients being treated with chemotherapy for acute leukemia (AL) or undergoing hematopoietic stem cell transplantation (HSCT) will decrease the incidence of bacteremia.
I. To determine the effect of prophylactic levofloxacin on resistance patterns of bacterial isolates from all sterile site cultures, and the evolution of antimicrobial resistance from peri-rectal swab isolates of Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus mitis.
II. To determine the effect of levofloxacin prophylaxis on total number of days of antibiotic administration (prophylactic, empiric, and treatment) in children undergoing therapy for AL or HSCT.
III. To determine whether levofloxacin prophylaxis reduces the incidence of fever with neutropenia, severe infection, and death from bacterial infection.
IV. To assess the safety of levofloxacin prophylaxis, with specific attention to musculoskeletal disorders including tendinopathy and tendon rupture.
V. To assess the impact of prophylactic levofloxacin on the incidence of Clostridium difficile-associated diarrhea (CDAD), and the incidence of microbiologically documented invasive fungal infections (IFI).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive levofloxacin orally (PO) or intravenously (IV) over 60-90 minutes once daily (QD) or twice daily (BID) beginning on day 3 during 2 consecutive courses of chemotherapy or beginning on day -2 during HSCT and continuing until blood counts recover.
ARM II: Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
After completion of study therapy, patients are followed up for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||624 participants|
|Intervention Model:||Parallel Assignment|
|Primary Purpose:||Supportive Care|
|Official Title:||A Randomized Trial of Levofloxacin to Prevent Bacteremia in Children Being Treated for Acute Leukemia (AL) or Undergoing Hematopoietic Stem Cell Transplantation (HSCT)|
|Actual Study Start Date :||September 2011|
|Actual Primary Completion Date :||June 2017|
|Actual Study Completion Date :||June 2017|
Experimental: 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.
Given PO or IV
No Intervention: Arm II (standard of care)
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 [ Time Frame: Up to 60 days after enrollment or receiving levofloxacin ]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.
- Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms [ Time Frame: Up to 60 days after enrollment or receiving levofloxacin ]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
- Comparison of the Percentage of Patients Having Incidence of Fever and Febrile Neutropenia Between Arms [ Time Frame: Up to 60 days after enrollment or receiving levofloxacin ]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.
- Comparison of the Percentage of Patients Having Severe Infection Between Arms [ Time Frame: Up to 60 days after enrollment or receiving levofloxacin ]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
- Comparison of the Percentage of Patients That Died Due to Bacterial Infection Between Arms [ Time Frame: Up to 60 days after enrollment or receiving levofloxacin ]
- Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms [ Time Frame: Enrollment, 2 months and 12 months post infection observation period ]Musculoskeletal conditions included at least one occurrence of arthralgia, arthritis, gait abnormality or tendinopathy.
- Comparison of the Percentage of Patients Having Incidence of CDAD Between Arms [ Time Frame: Up to 60 days after enrollment or receiving levofloxacin ]Clostridium Difficile Associated Disease (CDAD) is defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher.
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|Ages Eligible for Study:||6 Months to 21 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Patient must fit 1 of the following 2 categories:
Planned to receive at least 2 consecutive cycles (not required to be the first 2 cycles) of intensive chemotherapy for either:
- De novo, relapsed or secondary acute myeloid leukemia (AML), or acute leukemia of ambiguous lineage treated with standard AML therapy
- Relapsed acute lymphoblastic leukemia (ALL)
- For the purposes of this study, "intensive chemotherapy" is defined as regimens that are predicted by the local investigator to cause neutropenia for > 7 days; examples include, but are not limited to, treatment with "4-drug induction" (anthracycline, vincristine, asparaginase, and steroid), high dose cytarabine, anthracycline/cytarabine, ifosfamide/etoposide, and clofarabine-containing regimens
Stem cell transplantation patients
- Planned to receive at least 1 myeloablative autologous or allogeneic HSCT
- For the purposes of this study, myeloablative autologous and allogeneic HSCT are those in which the conditioning regimen is predicted by the local Investigator to cause neutropenia for > 7 days
Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows:
- 0.5 mg/dL (6 months to < 1 year of age)
- 0.6 mg/dL (1 to < 2 years of age)
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male)/1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male)/1.4 mg/dL (female) (>= 16 years of age)
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
- Patients previously enrolled on the trial are not eligible; therefore, patients with AL who were on study during intensive chemotherapy are not eligible to be enrolled during the HSCT
- Patients with an allergy to quinolones
- Patients with chronic active arthritis
- Patients with a known pathologic prolongation of the corrected QT (QTc)
- Females who are pregnant or breast feeding
Patients being treated with antibacterial agents, other than any of the following:
- Cotrimoxazole or other agents including dapsone, atovaquone, and pentamidine administered for Pneumocystitis jiroveci (PCP) prophylaxis
- Topical antibiotics
- Central venous catheter antibiotic lock therapy
- Note: prophylactic antifungal therapy is NOT an exclusion criterion
- Patients currently enrolled on the ACCL1034 study are not eligible until they have completed the 90 day observation period of that study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01371656
|Principal Investigator:||Sarah Alexander, MD||Children's Oncology Group|
Documents provided by Children's Oncology Group:
|Responsible Party:||Children's Oncology Group|
|Other Study ID Numbers:||
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 Posted:||June 13, 2011 Key Record Dates|
|Results First Posted:||June 26, 2018|
|Last Update Posted:||December 7, 2020|
|Last Verified:||June 2018|
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Immune System Diseases
Signs and Symptoms, Digestive
Bacterial Infections and Mycoses
Anti-Infective Agents, Urinary