Levofloxacin in Preventing Infection in Young Patients Receiving Chemotherapy For Acute Leukemia or Undergoing Stem Cell Transplantation
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.
Procedure: standard follow-up care
|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)|
- 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 ]
- 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 ]
|Study Start Date:||June 2011|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
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.
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
- 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.
- 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.