An Investigator Initiated, Phase II Single-Center, Randomized, Open-Label, Prospective, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftolozane-Tazobactam Plus Vancomycin, Linezolid Versus Standard of Care Plus Vancomycin, Linezolid as Empiric Therapy in Febrile Neutropenic Adults With Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Number of Participants With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)
研究概览
简要总结
The goal of this clinical research study is to learn if the study drug ceftolozane-tazobactam is more effective in controlling febrile neutropenia (fever and low white blood cell counts) than using approved antibiotics in patients with cancer. The safety of ceftolozane-tazobactam will also be studied.
This is an investigational study. Ceftolozane-tazobactam is FDA approved and commercially available to treat certain types of infections. It is not approved for the treatment of febrile neutropenia, either by itself or in combination with other antibiotics. Its use to treat febrile neutropenia is investigational.
All other antibiotics given on this study are FDA approved and commercially available for the treatment of infections. However, only cefepime is specifically FDA approved to treat febrile neutropenia. The study doctor can explain how the study drugs are designed to work.
Up to 100 participants will take part in this study. All will be enrolled at MD Anderson.
详细描述
Study Groups and Study Drug Administration:
If participant is found to be eligible to take part in this study and participant agrees, participant will be randomly assigned (as in the flip of a coin) to either receive either the study drug (Group 1) or a standard treatment antibiotic (Group 2). This is done because no one knows if one study group is better, the same, or worse than the other group. Both participant and the study doctor will know what participant is receiving.
If participant is in Group 1, participant will receive ceftolozane-tazobactam by vein over 1 hour every 8 hours.
If participant is in Group 2, participant will receive a standard treatment antibiotic. This may include one of the following 3 options:
cefepime by vein over about 30 minutes every 8 hours. meropenem by vein over about 30 minutes every 8 hours. piperacillin/tazobactam by vein over about 1 hour every 6 hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has provided written informed consent, and has the willingness and ability to comply with all study procedures
- •Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation; neutropenic fever is defined as the presence of neutropenia defined by: 1) absolute neutrophil count (ANC) < 500 cells/mm^3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as: 2) single oral temperature measurement of > 101 degree Fahrenheit (F) (38.3 degree Celsius [C]) or a temperature of > 100.4 degree F (38.0 degree C) sustained over a 1-hour period
- •Requires hospitalization for IV empiric antibiotic therapy
- •If female: not breastfeeding; agrees to not attempt to become pregnant during the study; is surgically sterile or at least 2-years postmenopausal, or if of childbearing potential, has negative screening serum pregnancy test (if serum pregnancy test results are not available at the time of enrollment, a negative urine pregnancy test is required within 24 hours.); if of childbearing potential (including being < 2 years postmenopausal), is willing to practice sexual abstinence or use an effective dual form of contraception with her partner (eg, 2 barrier methods, barrier method plus hormonal method) during treatment and for ≥ 28 days after the last dose of any study therapy (IV or oral)
排除标准
- •History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic or tazobactam
- •Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or blood product administration)
- •Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with pneumonia) that justifies adding additional empiric antimicrobial therapy (eg, antifungals)
- •Confirmed viral infection that justifies adding additional empiric antiviral therapy (eg, ganciclovir, foscarnet)
- •Known acute viral hepatitis
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 5 times the upper limit of normal (x ULN); patients with values > 3 x ULN and < 5 x ULN are eligible if the value is acute and directly related to the infectious process being treated
- •Total bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert disease; manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy
- •Known to be human immunodeficiency virus positive
- •Severely impaired renal function, defined as creatinine clearance (CrCl) =< 30 mL/min estimated by the Cockcroft-Gault formula
- •Expected requirement for hemodialysis while on study therapy
- •Received > 24 hours of IV antibacterial therapy (with study drugs) within 72 hours of the initiation of inpatient IV study drug for treatment of suspected infection; antibiotic prophylaxis and oral antibiotics is allowed; prophylactic use of antiviral or antifungal medication is permitted
- •Requirement for any non-study potentially effective concomitant systemic antibacterial therapy
- •Past or current history of epilepsy or seizure disorder; exception: well-documented febrile seizure of childhood
- •Evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid replacement)
- •Unable or unwilling to adhere to the study-specified procedures and restrictions
- •Any condition that would make the patient, in the opinion of the investigator, unsuitable for the study (eg, would place a patient at risk or compromise the quality of the data
- •Participation in any other ongoing ceftolozane/tazobactam trial
研究组 & 干预措施
Group I (ceftolozane-tazobactam)
Participants receive ceftolozane-tazobactam IV over 1 hour every 8 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. After at least 3 days, participants may switch to different PO or IV antibiotics at the discretion of the study doctor.
干预措施: Ceftolozane (Drug)
Group I (ceftolozane-tazobactam)
Participants receive ceftolozane-tazobactam IV over 1 hour every 8 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. After at least 3 days, participants may switch to different PO or IV antibiotics at the discretion of the study doctor.
干预措施: Laboratory Biomarker Analysis (Other)
Group I (ceftolozane-tazobactam)
Participants receive ceftolozane-tazobactam IV over 1 hour every 8 hours for up to 14 days in the absence of disease progression or unacceptable toxicity. After at least 3 days, participants may switch to different PO or IV antibiotics at the discretion of the study doctor.
干预措施: Tazobactam (Drug)
Group II (standard of care antibiotic treatment)
Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cefepime (Drug)
Group II (standard of care antibiotic treatment)
Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Group II (standard of care antibiotic treatment)
Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Meropenem (Drug)
Group II (standard of care antibiotic treatment)
Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Piperacillin-Tazobactam (Drug)
Group II (standard of care antibiotic treatment)
Participants receive standard of care antibiotic treatment consisting of either cefepime IV over 30 minutes every 8 hours, meropenem IV over 30 minutes every 8 hours, or piperacillin-tazobactam IV over 1 hour every 6 hours for up to 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Tazobactam (Drug)
结局指标
主要结局
Number of Participants With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)
时间窗: Within 72 hours after administration of the last dose of inpatient IV study drug
Resolution of all acute signs and symptoms of the primary infection or improvement to such an extent that no additional antibacterial therapy is required (ie, except for protocol-allowed adjunctive therapies and/or oral or IV switch) and such that no more than 14 days of total antibacterial therapy is required.
次要结局
- Number of Participants With Favorable Clinical Response in the ME Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Number of Participants With Favorable Clinical Response in the ME Analysis Set at TOC(21 to 28 days after the start of inpatient IV study drug.)
- Number of Participants With Favorable Clinical Response in the ME Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Clinical Response in the Microbiological Modified Intent-to-treat (mMITT) Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Number of Participants With Favorable Clinical Response in the Clinically Evaluable (CE) Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug.)
- Number of Participants With Favorable Clinical Response in the MITT Analysis Set at TOC(21 to 28 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Clinical Response in the MITT Analysis Set at Late Follow-Up (LFU)(35 to 42 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Test of Cure (TOC)(21 to 28 days after the start of inpatient IV study drug.)
- Number of Participants With Favorable Clinical Response in the mMITT Analysis Set at Late Follow-Up (LFU)(35 to 42 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Clinical Response in the CE Analysis Set at TOC(21 to 28 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Clinical Response in the CE Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Microbiological Response in the mMITT Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug)
- Favorable Microbiological Response in the mMITT Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Microbiological Response in the mMITT Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug.)
- Number of Participants With Favorable Microbiological Response in the ME Analysis Set at EOIV.(Within 72 hours after administration of the last dose of inpatient IV study drug)
- Number of Participants With Favorable Microbiological Response in the ME Analysis Set at TOC.(21 to 28 days after the start of inpatient IV study drug)
- Number of Participants With Favorable Microbiological Response in the ME Analysis Set at LFU(35 to 42 days after the start of inpatient IV study drug)
- Number of Participants With Infection-related Mortality in the MITT Analysis Set at TOC(21 to 28 days after the start of inpatient IV study drug)
- Number of Participants With Infection-related Mortality in the MITT Analysis Set at LFU(35 to 42 days after the start of inpatient IV study drug)
- Number of Participants With Infection-related Mortality the mMITT Analysis Set at TOC(21 to 28 days after the start of inpatient IV study drug)
- Number of Participants With Infection-related Mortality in the mMITT Analysis Set at LFU.(35 to 42 days after the start of inpatient IV study drug)
- 30 Day All-cause Mortality in the MITT Analysis Set(30 days after the last dose of inpatient IV study drug)
- 30 Day All-cause Mortality in the mMITT Analysis Set(30 days after the last dose of inpatient IV study drug)