Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation - Full Text View

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:

Genetics Home Reference related topics: core binding factor acute myeloid leukemia cyclic neutropenia cytogenetically normal acute myeloid leukemia familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Bacterial Infections Diarrhea Leukemia

Drug Information available for: Ofloxacin Levofloxacin Ofloxacin hydrochloride

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Acute Lymphoblastic Leukemia Granulocytopenia Childhood Acute Lymphoblastic Leukemia Acute Leukemia of Ambiguous Lineage Lymphosarcoma

U.S. FDA Resources

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:	December 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 (Child, Adult)
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

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Sarah Alexander, MD	Children's Oncology Group

More Information


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:	April 8, 2016
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Leukemia Infection Communicable Diseases Leukemia, Myeloid Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Diarrhea Acute Disease Bacterial Infections Neutropenia Mycoses Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders	Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Signs and Symptoms, Digestive Signs and Symptoms Disease Attributes Pathologic Processes Agranulocytosis Leukopenia Leukocyte Disorders Hematologic Diseases Levofloxacin Ofloxacin Anti-Infective Agents, Urinary Anti-Infective Agents

ClinicalTrials.gov processed this record on September 29, 2016