Trial record 1 of 1 for:    COG ACCL0934
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Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01371656
First received: June 4, 2011
Last updated: August 5, 2014
Last verified: August 2014
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Susceptibility of S. mitis peri-rectal swab isolates to cefepime, levofloxacin, and penicillin [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Presence of carbapenem-resistant Enterobacteriaceae [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Resistance patterns for the gastrointestinal isolates colonizing each patient [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Resistance patterns of bacterial isolates from all sterile site cultures [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Duration of parenteral antibiotic administration [ Time Frame: During 2 courses of chemotherapy or 1 transplantation procedure ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Primary Completion Date: June 2016 (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
Genders Eligible for Study:   Both
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

  Show 89 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Sarah Alexander Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01371656     History of Changes
Other Study ID Numbers: ACCL0934, NCI-2011-02636, CDR0000695661, ACCL0934, COG-ACCL0934, ACCL0934, U10CA095861
Study First Received: June 4, 2011
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014