Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
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.
Accelerated Phase Chronic Myelogenous Leukemia
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
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)
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
High Risk Metastatic Gestational Trophoblastic Tumor
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Plasma Cell Neoplasm
Previously Treated Childhood Rhabdomyosarcoma
Previously Treated Myelodysplastic Syndromes
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Malignant Testicular Germ Cell Tumor
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Ovarian Epithelial Cancer
Recurrent Ovarian Germ Cell Tumor
Recurrent Small Lymphocytic Lymphoma
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Splenic Marginal Zone Lymphoma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage II Ovarian Epithelial Cancer
Stage II Ovarian Germ Cell Tumor
Stage III Childhood Hodgkin Lymphoma
Stage III Childhood Large Cell Lymphoma
Stage III Childhood Lymphoblastic Lymphoma
Stage III Childhood Small Noncleaved Cell Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Malignant Testicular Germ Cell Tumor
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Ovarian Epithelial Cancer
Stage III Ovarian Germ Cell Tumor
Stage III Small Lymphocytic Lymphoma
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Stage IV Childhood Hodgkin Lymphoma
Stage IV Childhood Large Cell Lymphoma
Stage IV Childhood Lymphoblastic Lymphoma
Stage IV Childhood Small Noncleaved Cell Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Ovarian Epithelial Cancer
Stage IV Ovarian Germ Cell Tumor
Stage IV Small Lymphocytic Lymphoma
Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Procedure: standard follow-up care
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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 among AL and HSCT subjects, respectively [ Time Frame: During 2 courses of chemotherapy (up to 60 days each) or 1 transplantation procedure ] [ Designated as safety issue: No ]Compared between arms using the Chi-square test. Evaluated using 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 [ Time Frame: At the start and end of each treatment period ] [ Designated as safety issue: No ]Observed incidence rate will be compared between the 2 randomized arms.
- Incidence of febrile neutropenia, severe infection, and death from bacterial infection [ Time Frame: Assessed 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.
- Safety of levofloxacin with special attention to musculoskeletal disorders, particularly tendinopathy and tendon rupture [ Time Frame: Assessed up to 1 year ] [ Designated as safety issue: Yes ]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. Assessed by the NCI CTCAE v. 4.0.
- 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 CDAD, defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, Grade 2 and higher [ Time Frame: Assessed 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.
|Study Start Date:||June 2011|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm I (antibiotic)
Patients receive levofloxacin 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 HSCT and continuing until blood counts recover.
Given PO or IV
Active Comparator: Arm II (standard care)
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
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.
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 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: 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 intravenously (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 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.