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.
Verified February 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: February 5, 2014
Last verified: February 2014

June 4, 2011
February 5, 2014
June 2011
June 2016   (final data collection date for primary outcome measure)
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.
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 ]
Complete list of historical versions of study NCT01371656 on ClinicalTrials.gov Archive Site
  • Susceptibility of E. coli, K. pneumoniae, and P. aeruginosa to cefepime, imipenem, and levofloxacin [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Susceptibility of S. mitis 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 ]
  • 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, severe infection, and 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 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 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.
  • 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 ]
Not Provided
Not Provided
 
Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
A Randomized Trial of Levofloxacin to Prevent Bacteremia in Children Being Treated for Acute Leukemia (AL) or Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

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.

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 1.

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Supportive Care
  • 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
Given PO or IV
Other Names:
  • Levaquin
  • Quixin
  • 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 1.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
592
Not Provided
June 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient must fit 1 of the following 2 categories:

    • Chemotherapy patients

      • Scheduled to receive at least 2 consecutive courses (not required to be the first 2 courses) 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 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)
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2

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
Both
6 Months to 21 Years
No
Not Provided
United States,   Canada
 
NCT01371656
ACCL0934, NCI-2011-02636, CDR0000695661, ACCL0934, COG-ACCL0934, ACCL0934, U10CA095861
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Sarah Alexander Children's Oncology Group
Children's Oncology Group
February 2014

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