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

This study is currently recruiting participants.
Verified July 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01371656
First received: June 4, 2011
Last updated: July 12, 2012
Last verified: July 2012
History of Changes
  Purpose

RATIONALE: 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.

PURPOSE: This randomized phase III trial studies how well levofloxacin works in preventing infection in young patients receiving chemotherapy for acute leukemia or undergoing stem cell transplant.


Condition Intervention Phase
Bacterial Infection
Leukemia
Musculoskeletal Complications
Neutropenia
 Drug: levofloxacin
Procedure: standard follow-up care
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Single Blind
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:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • Incidence of febrile neutropenia, severe infection, and death from bacterial infection [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: Yes ]
  • Duration of parenteral antibiotic administration during 2 courses of chemotherapy or 1 transplantation procedure [ Designated as safety issue: No ]

Estimated Enrollment: 532
Study Start Date: June 2011
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive levofloxacin orally (PO) or IV over 60-90 minutes once or twice daily beginning on day 1 during 2 consecutive courses of chemotherapy or beginning on day -2 during hematopoietic stem cell transplantation (HSCT) and continuing until blood counts recover.
 Drug: levofloxacin
Given PO or IV
No Intervention: Arm II
Patients receive established standard of care and receive chemotherapy or HSCT as patients in arm 1.
 Procedure: standard follow-up care
Established standard of care

Detailed Description:

OBJECTIVES:

Primary

  • 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

  • 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 Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Streptococcus mitis.
  • 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.
  • To determine whether levofloxacin prophylaxis reduces the incidence of fever with neutropenia, severe infection, and death from bacterial infection.
  • To assess the safety of levofloxacin prophylaxis, with specific attention to musculoskeletal disorders including tendinopathy and tendon rupture.
  • 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: This is a multicenter study. Patients are stratified according to diagnosis (de novo acute myeloid leukemia [AML] vs secondary AML vs relapsed AML vs relapsed acute lymphoblastic leukemia [ALL]), and therapy (undergoing autologous HSCT vs undergoing allogeneic HSCT). Patients are randomized to 1 of 2 treatment groups.

  • Arm I: Patients receive levofloxacin orally (PO) or IV over 60-90 minutes once or twice daily beginning on day 1 during 2 consecutive courses of chemotherapy or beginning on day -2 during hematopoietic stem cell transplantation (HSCT) and continuing until blood counts recover.
  • Arm II: Patients receive established standard of care and receive chemotherapy or HSCT as patients in arm 1.

Musculoskeletal assessment is conducted at baseline and at 2 and 12 months.

Patients may undergo perirectal or stool swab collection for ancillary studies.

After completion of study therapy, patients are followed up for 1 year.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Patients must fit 1 of the following categories:

    • Chemotherapy patients

      • Scheduled to receive at least 2 consecutive courses (not required to be the first 2 courses) of intensive chemotherapy for de novo, relapsed, or secondary acute myeloid leukemia (AML), or 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 including, but not limited to:

        • Treatment with "4-drug induction" (anthracycline, vincristine, asparaginase, and steroid)
        • High-dose cytarabine, anthracycline/cytarabine, or ifosfamide/etoposide
        • Clofarabine-containing regimens

    • Stem cell transplantation patients*

      • Scheduled to receive at least 1 myeloablative autologous or allogeneic hematopoietic stem cell transplantation (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 NOTE: *Patients with AML or ALL who were enrolled on this study during intensive chemotherapy are not eligible to be enrolled during HSCT.

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2

  • Creatinine clearance or radioisotope GFR > 70 mL/min OR serum creatinine based on age and/or 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) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
  • No patients with an allergy to quinolones
  • No patients with chronic active arthritis
  • No patients with a known pathologic prolongation of the QTc
  • No females who are pregnant or breast feeding

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No patients scheduled to receive non-intensive or palliative chemotherapy
  • No patients undergoing non-myeloablative hematopoietic stem cell transplantation (HSCT)
  • No patients being treated with antibacterial agents, other than cotrimoxazole for Pneumocystitis jiroveci (PCP) prophylaxis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01371656

  Show 51 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Sarah Alexander, MD The Hospital for Sick Children
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT01371656     History of Changes
Other Study ID Numbers: CDR0000695661, COG-ACCL0934
Study First Received: June 4, 2011
Last Updated: July 12, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
bacterial infection
musculoskeletal complications
neutropenia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with del(5q)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
 adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary acute myeloid leukemia
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
recurrent childhood acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Bacterial Infections
Leukemia
Neutropenia
Neoplasms by Histologic Type
Neoplasms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Ofloxacin
 Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on June 13, 2013