Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE June 4, 2011
First Posted Date  ICMJE June 13, 2011
Results First Submitted Date  ICMJE May 25, 2018
Results First Posted Date  ICMJE June 25, 2018
Last Update Posted Date July 24, 2018
Actual Study Start Date  ICMJE September 2011
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 10, 2011)
Occurrence of at least 1 episode of true bacteremia during the study timeframe of 2 courses of chemotherapy or 1 transplant procedure among AL and HSCT subjects, respectively
Change History Complete list of historical versions of study NCT01371656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2011)
  • Susceptibility of E. coli, K. pneumoniae, and P. aeruginosa to cefepime, imipenem, and levofloxacin and the susceptibility of S. mitis to cefepime, levofloxacin, and penicillin at the start and end of each treatment period
  • Incidence of febrile neutropenia, severe infection, and death from bacterial infection
  • Safety of levofloxacin with special attention to musculoskeletal disorders, particularly tendinopathy and tendon rupture, as assessed by CTCAE v. 4.0 every 6 months for 2 years and annually thereafter
  • Duration of parenteral antibiotic administration during 2 courses of chemotherapy or 1 transplantation procedure
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
Official Title  ICMJE A Randomized Trial of Levofloxacin to Prevent Bacteremia in Children Being Treated for Acute Leukemia (AL) or Undergoing Hematopoietic Stem Cell Transplantation (HSCT)
Brief Summary This randomized phase III trial studies how well levofloxacin works in preventing infection in young patients with acute leukemia receiving chemotherapy or undergoing stem cell transplant. Giving antibiotics may be effective in preventing or controlling early infection in patients receiving chemotherapy or undergoing stem cell transplant for acute leukemia. It is not yet known whether levofloxacin is effective in preventing infection.
Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Primary Purpose: Supportive Care
Condition  ICMJE
  • 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  ICMJE Drug: levofloxacin
Given PO or IV
Other Names:
  • Levaquin
  • Quixin
Study Arms  ICMJE
  • 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.
    Intervention: Drug: levofloxacin
  • No Intervention: Arm II (standard of care)
    Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 7, 2018)
624
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2011)
532
Actual Study Completion Date  ICMJE June 2017
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient must fit 1 of the following 2 categories:

    • Chemotherapy patients

      • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01371656
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Sarah Alexander, MD Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP