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

NCT ID: NCT01371656

Last Updated: 2020-12-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

624 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-09-30

Study Completion Date

2017-06-30

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Study Groups

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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.

Group Type EXPERIMENTAL

levofloxacin

Intervention Type DRUG

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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levofloxacin

Given PO or IV

Intervention Type DRUG

Other Intervention Names

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Levaquin Quixin

Eligibility Criteria

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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
Minimum Eligible Age

6 Months

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sarah Alexander, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

City of Hope Medical Center

Duarte, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Miller Children's Hospital

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lombardi Comprehensive Cancer Center at Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Saint Mary's Hospital

West Palm Beach, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Georgia Regents University

Augusta, Georgia, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Saint Vincent Hospital and Health Services

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Children's Hospital-Main Campus

New Orleans, Louisiana, United States

Site Status

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Michigan State University - Breslin Cancer Center

Lansing, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Saint John's Mercy Medical Center

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Saint Peter's University Hospital

New Brunswick, New Jersey, United States

Site Status

UMDNJ - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Ny Cancer%

Valhalla, New York, United States

Site Status

Mission Hospital-Memorial Campus

Asheville, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

The Children's Medical Center of Dayton

Dayton, Ohio, United States

Site Status

The Toledo Hospital/Toledo Children's Hospital

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Palmetto Health Richland

Columbia, South Carolina, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Childrens Hospital-King's Daughters

Norfolk, Virginia, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

Marshfield Clinic

Marshfield, Wisconsin, United States

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Janeway Child Health Centre

St. John's, Newfoundland and Labrador, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

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NCI-2011-02636

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000695661

Identifier Type: OTHER

Identifier Source: secondary_id

ACCL0934

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ACCL0934

Identifier Type: OTHER

Identifier Source: secondary_id

ACCL0934

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA095861

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACCL0934

Identifier Type: -

Identifier Source: org_study_id