Brief Summary
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.
Brief Title
Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
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
Eligibility 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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
21 Years
Minimum Age
6 Months
NCT Id
NCT01371656
Org Class
Network
Org Full Name
Children's Oncology Group
Org Study Id
ACCL0934
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
A bacteremia incidence is defined as an occurrence of at least 1 episode of true (centrally reviewed) bacteremia among Acute Leukemia (AL) and Hematopoietic stem cell transplantation (HSCT) patients.
Outcome Measure
Comparison of the Percentage of Patients Having Bacteremia Incidence Between Levofloxacin vs. No Prophylaxis Arms
Outcome Time Frame
Up to 60 days after enrollment or receiving levofloxacin
Secondary Ids
Secondary Id
NCI-2011-02636
Secondary Id
CDR0000695661
Secondary Id
ACCL0934
Secondary Id
COG-ACCL0934
Secondary Id
ACCL0934
Secondary Id
U10CA095861
Secondary Outcomes
Outcome Description
Exposure to antibiotics was considered during the infection observation period(s) was defined a priori as follows: Gram positive agents = vancomycin, linezolid, daptomycin or quinupristin/dalfopristin; Aminoglycosides = amikacin, gentamicin or tobramycin; Third or fourth generation cephalosporins = cefepime, ceftazidime, ceftriaxone or cefotaxime; Empiric antibiotics for fever and neutropenia = imipenem, meropenem, cefepime, ceftazidime or piperacillin/tazobactam
Outcome Time Frame
Up to 60 days after enrollment or receiving levofloxacin
Outcome Measure
Comparison of the Percentage of Patients Having Antibiotic Exposures Between Arms
Outcome Description
Fever and febrile neutropenia defined as Absolute Neutrophil Count (ANC) \< 1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of \>= 38 degrees C (100.4 degrees F) for more than one hour.
Outcome Time Frame
Up to 60 days after enrollment or receiving levofloxacin
Outcome Measure
Comparison of the Percentage of Patients Having Incidence of Fever and Febrile Neutropenia Between Arms
Outcome Description
Severe infection defined as any grade 4 or 5 CTCAE catheter-related infection, enterocolitis, lung infection, sepsis, small intestine infection and other infections or infestations
Outcome Time Frame
Up to 60 days after enrollment or receiving levofloxacin
Outcome Measure
Comparison of the Percentage of Patients Having Severe Infection Between Arms
Outcome Time Frame
Up to 60 days after enrollment or receiving levofloxacin
Outcome Measure
Comparison of the Percentage of Patients That Died Due to Bacterial Infection Between Arms
Outcome Description
Musculoskeletal conditions included at least one occurrence of arthralgia, arthritis, gait abnormality or tendinopathy.
Outcome Time Frame
Enrollment, 2 months and 12 months post infection observation period
Outcome Measure
Comparison of the Percentage of Patients Having Incidence of Musculoskeletal Adverse Events Including Tendinopathy (Tendonitis and Tendon Rupture) Between Arms
Outcome Description
Clostridium Difficile Associated Disease (CDAD) is defined as a positive C. difficile toxin assay result and diarrhea, CTCAE version 4, grade 2 and higher.
Outcome Time Frame
Up to 60 days after enrollment or receiving levofloxacin
Outcome Measure
Comparison of the Percentage of Patients Having Incidence of CDAD Between Arms
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
21
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Lisa Gennarini
Investigator Email
lfigueir@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
Digestive System --- SIGNS AND SYMPTOMS, DIGESTIVE
MeSH Terms
LEUKEMIA, BIPHENOTYPIC, ACUTE
BACTERIAL INFECTIONS
DIARRHEA
MYCOSES
NEUTROPENIA
PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
LEUKEMIA, LYMPHOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
BACTERIAL INFECTIONS AND MYCOSES
INFECTIONS
SIGNS AND SYMPTOMS, DIGESTIVE
SIGNS AND SYMPTOMS
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
AGRANULOCYTOSIS
LEUKOPENIA
CYTOPENIA
LEUKOCYTE DISORDERS
LEVOFLOXACIN
OFLOXACIN
FLUOROQUINOLONES
4-QUINOLONES
QUINOLONES
QUINOLINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS