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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01371656
First received: June 4, 2011
Last updated: July 10, 2017
Last verified: July 2017
  Purpose
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.

Condition Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (masked role unspecified)
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)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Occurrence of at least 1 episode of true bacteremia among AL and HSCT subjects, respectively [ Time Frame: Up to 60 days ]
    Compared between arms using the Chi-square test. Evaluated using logistic regression models.


Secondary Outcome Measures:
  • Susceptibility of E. coli, K. pneumoniae, and P. aeruginosa stool or peri-rectal swab isolates to cefepime, imipenem, and levofloxacin [ Time Frame: Up to 1 year ]
  • Susceptibility of S. mitis peri-rectal swab isolates to cefepime, levofloxacin, and penicillin [ Time Frame: Up to 1 year ]
  • Presence of carbapenem-resistant Enterobacteriaceae [ Time Frame: Up to 1 year ]
  • Resistance patterns for the gastrointestinal isolates colonizing each patient [ Time Frame: Up to 1 year ]
  • Resistance patterns of bacterial isolates from all sterile site cultures [ Time Frame: Up to 1 year ]
  • Duration of parenteral antibiotic administration [ Time Frame: During 2 courses of chemotherapy or 1 transplantation procedure ]
    Compared between the 2 arms using 2-sample t-test. Wilcoxon rank sum test will also be considered. Estimated using linear regression models.

  • Incidence of febrile neutropenia [ Time Frame: Up to 1 year ]
    Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0.

  • Incidence of severe infection [ Time Frame: Up to 1 year ]
    Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the NCI CTCAE v. 4.0.

  • Incidence of death from bacterial infection [ Time Frame: Up to 1 year ]
    Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the NCI CTCAE v. 4.0.

  • Incidence of musculoskeletal adverse events [ Time Frame: Up to 1 year ]
    Compared between arms using the Chi-square test. Evaluated using logistic regression models. Graded using the NCI CTCAE v. 4.0.

  • Incidence of tendinopathy (tendonitis and tendon rupture) [ Time Frame: Up to 1 year ]
    Separate levofloxacin patients into those with/without concurrent steroid use and comparing them separately to control patients, or adjusting for concurrent steroid use as covariate in logistic regression models.

  • Incidence of CDAD, defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher [ Time Frame: Up to 1 year ]
    Compared by separating levofloxacin patients into those with/without concurrent steroid use or adjusting for concurrent steroid use as a covariate in logistic regression models.


Estimated Enrollment: 740
Study Start Date: June 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: levofloxacin
Given PO or IV
Other Names:
  • Levaquin
  • Quixin
No Intervention: Arm II (standard of care)
Patients receive established standard of care and receive chemotherapy or HSCT as patients in Arm I.

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.

  Eligibility

Ages Eligible for Study:   6 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371656

  Hide Study Locations
Locations
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202-3591
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
City of Hope Medical Center
Duarte, California, United States, 91010
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Miller Children's Hospital
Long Beach, California, United States, 90806
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, D.C., District of Columbia, United States, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, D.C., District of Columbia, United States, 20057
United States, Florida
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States, 33908
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207-8426
Nemours Children's Hospital
Orlando, Florida, United States, 32827
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Mary's Hospital
West Palm Beach, Florida, United States, 33407
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Illinois
University of Illinois
Chicago, Illinois, United States, 60612
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, United States, 60453
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States, 46260
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
Children's Hospital-Main Campus
New Orleans, Louisiana, United States, 70118
Ochsner Medical Center
New Orleans, Louisiana, United States, 70121
United States, Maryland
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
United States, Massachusetts
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, United States, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
Michigan State University - Breslin Cancer Center
Lansing, Michigan, United States, 48910
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, Nebraska
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Saint Peter's University Hospital
New Brunswick, New Jersey, United States, 08901
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York University Langone Medical Center
New York, New York, United States, 10016
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14642
Montefiore Medical Center
The Bronx, New York, United States, 10467-2490
Ny Cancer%
Valhalla, New York, United States, 10595
United States, North Carolina
Mission Hospital-Memorial Campus
Asheville, North Carolina, United States, 28801
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
The Toledo Hospital/Toledo Children's Hospital
Toledo, Ohio, United States, 43606
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, United States, 18017
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-2001
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
United States, South Dakota
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States, 57117-5134
United States, Texas
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Virginia
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
Madigan Army Medical Center
Tacoma, Washington, United States, 98431
United States, Wisconsin
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Newfoundland and Labrador
Janeway Child Health Centre
Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada, H3H 1P3
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sarah Alexander, MD Children's Oncology Group
  More Information

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 )
Study First Received: June 4, 2011
Last Updated: July 10, 2017

Additional relevant MeSH terms:
Leukemia
Infection
Communicable Diseases
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Diarrhea
Neutropenia
Acute Disease
Bacterial Infections
Mycoses
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Disease Attributes
Pathologic Processes
Levofloxacin
Ofloxacin
Anti-Infective Agents, Urinary
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 27, 2017