Symptoms and General Pathology

Wounds and Injuries

All Conditions

Hyperthermia

Fever

Anti-Infective Agents

All Drugs and Chemicals

Anti-Bacterial Agents

Vancomycin

Meropenem

Tazobactam

Piperacillin

Piperacillin, Tazobactam Drug Combination

Cefepime

Lactams

beta-Lactams

Linezolid

Daptomycin

Imipenem

Cilastatin, Imipenem Drug Combination

Cilastatin

Relebactam

beta-Lactamase Inhibitors

Enzyme Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes q6h for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h. Patients may continue to receive imipenem/cilastatin/relebactam IVover 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.

Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.

Imipenem/Cilastatin/Relebactam

Piperacillin-Tazobactam

Issam I Raad

This phase II trial studies the effect of imipenem-relebactam in treating patients with cancer who have a fever due to low white blood cell counts (febrile neutropenia). In this study, imipenem-relebactam will be compared to the standard-of-care treatment (cefepime, meropenem, or piperacillin/tazobactam) for the treatment of febrile neutropenia. Imipenem-relebactam is used to treat infections. Giving imipenem-relebactam may help to control febrile neutropenia in patients with cancer.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of imipenem, cilastatin sodium, and relebactam monohydrate (imipenem-relebactam) plus vancomycin, daptomycin or linezolid versus (vs) standard of care (SOC) plus vancomycin, daptomycin or linezolid as empiric therapy in febrile neutropenic adults with cancer with respect to favorable clinical response at end of inpatient intravenous therapy (EOIV) in the modified intent-to-treat (MITT) analysis set.

II. To evaluate the safety and tolerability of imipenem-relebactam plus vancomycin, daptomycin, or linezolid compared with SOC plus vancomycin, daptomycin or linezolid as empiric therapy in febrile neutropenic adults with cancer.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of imipenem-relebactam plus vancomycin, daptomycin or linezolid compared with SOC plus vancomycin \< daptomycin or linezolid as empiric therapy in febrile neutropenic adults with cancer with respect to the following:

Ia. Favorable clinical response at EOIV in the mMITT and clinically evaluable (CE) analysis sets.

Ib. Favorable clinical response at time of clinical response (TOC) (ie, 21 to 28 days after start of intravenous \[IV\] therapy) and late follow-up (LFU) (ie, 35 to 42 days after start of IV therapy) in the MITT analysis set.

Ic. Favorable clinical response by baseline Gram-negative pathogen at EOIV, TOC, and LFU in the mMITT and CE analysis sets.

Id. Favorable microbiological response by patient and by baseline Gram-negative pathogen at EOIV, TOC, and LFU in the mMITT and ME analysis sets.

Ie. Infection-related mortality rate at TOC and LFU in the MITT and mMITT analysis sets.

If. 30-day all-cause mortality rate in the MITT and mMITT analysis sets. II. To evaluate the role of procalcitonin (PCT) in promoting antimicrobial stewardship resulting in the switch of most patients from the broad spectrum agents (Imipenem/Relebactam \& SOC) to a more simplified IV or oral antibiotic therapy in 48-72 hours.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I (TREATMENT): Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or orally (PO) q12h. Patients may continue to receive imipenem/cilastatin/relebactam IV over 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.

GROUP II (STANDARD OF CARE): Patients receive cefepime IV q8h for a minimum of 6 doses, meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. Patients may also receive gram-positive therapy at the discretion of the primary team or emergency center physician consisting of vancomycin IV q12h or linezolid IV or PO q12h.

Patients in both groups may receive other additional therapy (double-gram negative therapy) consisting of tobramycin IV q24h, amikacin IV q24h, ciprofloxacin IV q8h, minocycline q12h, tigecycline on days 1-2 q12h, doxycycline q12h, and/or bactrim. After at least 48 hours of gram-negative antimicrobial therapy, patients may be allowed to switch to PO or IV therapy such as linezolid PO, ampicillin, amoxicillin, amoxicillin/clavulanate PO, minocycline PO, ciprofloxacin PO, levofloxacin PO, cefpodoxime PO, trimethoprim/sulfamethoxazole PO, ceftriaxone IV, ertapenem IV, daptomycin IV and/or vancomycin IV for outpatient or home administration as clinically indicated. While in the hospital, patients undergo the collection of blood samples daily for 2 weeks, and urine samples every 2 days for up to 2 weeks.

After completion of study treatment, patients are followed up at 2, 21-28, and 35-42 days.

PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN

An Investigator Initiated, Phase II Single-Center, Randomized, Open-Label, Prospective, Study To Determine The Impact Of Serial Procalcitonin On Improving Antimicrobial Stewardship And On The Efficacy, Safety, And Tolerability Of Imipenem-Cilastatin-Relebactam Plus/Minus Vancomycin Or Linezolid Versus Standard Of Care Antipseudomonal Beta-Lactams Plus/Minus Vancomycin Or Linezolid As Empiric Therapy In Febrile Neutropenic Adults With Cancer

The primary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the CE (Clinically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The clinical outcome has three categories: Favorable clinical response, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at test-of-cure (TOC). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable clinical response of the patients in the ME (Microbiologically Evaluable) Analysis Set at late follow-up (LFU). The clinical outcome has three categories: Clinical cure, Clinical failure, and Indeterminate.

The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at end of inpatient intravenous therapy (EOIV). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

The secondary efficacy outcome is favorable microbiological response of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

The secondary efficacy outcome is favorable microbiological response of the patients in the ME (Microbiologically Evaluable) Analysis Set at end of inpatient intravenous therapy (EOIV). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

The secondary efficacy outcome is favorable microbiological response of the patients in the ME (Microbiologically Evaluable) Analysis Set at test-of-cure (TOC). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

The secondary efficacy outcome is favorable microbiological response of the participants in the ME (Microbiologically Evaluable) Analysis Set at late follow-up (LFU). The microbiological response outcome has five categories: Persistence, eradication, presumed eradication, presumed persistence, and Indeterminate.

The secondary efficacy outcome is infection-related mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC).

The secondary efficacy outcome is infection-related mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set at late follow-up (LFU).

The secondary efficacy outcome is Infection-related mortality of the participants in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at test-of-cure (TOC).

The secondary efficacy outcome is Infection-related mortality of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set at late follow-up (LFU).

The secondary efficacy outcome is 30-day all-cause mortality of the patients in the MITT (Modified Intent-To-Treat) Analysis Set.

The secondary efficacy outcome is 30-day all-cause mortality of the patients in the mMITT (Microbiological Modified Intent-To-Treat) Analysis Set.

Merck Sharp & Dohme LLC

M.D. Anderson Cancer Center

Per protocol, all SAEs were collected and reported according to the clinicaltrials.gov definitions.

Per protocol, all AEs of any grade that are possibly, probably and definitely related to the study drug, and any AE grade 3 or above regardless of their attribution to study drug were collected and reported. Therefore, other AEs, not required per protocol, were not collected.

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy.

Imipenem-Relebactam Arm

Patients receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may receive other additional therapy.

Group II (Cefepime, Meropenem, Piperacillin/Tazobactam)

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may continue on the study drug for up to 14 days. Participants may receive other addtional therapy.

Standard of Care (SOC) Arm

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

Hispanic or Latino

Middle East

White

Others

Race/Ethnicity, Customized

United States

Region of Enrollment

Hematological malignancy

Solid tumor

Type of Cancer

History of BMT within one year

Autologous

Allogeniec

Matched unrelated donor

HLA matched related

GVHD

Type of allogeneic transplant

< 36

36-38

> 38

Temperature at initial presentation (oC)

No sepsis

Sepsis

Severe sepsis

Sepsis status

Neurologic impairment

Confusion

Clinical source presentation

Head and neck

Lung (pneumonia)

Abdomen

Genitourinary

Skin and soft tissue

Site of clinical presentation

Microbiological documentation (positivity)

Blood

Site of organism

Organisms identified

Gram negative

Gram positive

Both Gram Positive and Gram Negative

Organisms recovered in positive cultures

Enterobacter cloacae

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeruginosa

Rhizobium radiobacter

Klebsiella pneumoniae & Enterococcus faecalis

Haemophilus parainfluenzae & Streptococcus mitis/oralis Group

Pseudomonas aeruginosa, Streptococcus mitis/oralis Group & Enterococcus faecalis

Roseomonas mucosa, Micrococcus luteus & Dermacoccus nishinomiyaensis

Enterococcus faecium

Staphylococcus epidermidis

Streptococcus mitis/oralis group

Enterococcus faecalis & Rothia mucilaginosa

Bacteremia

CVC being the source of BSI isolation

Piperacillin/tazobactam

SOC Antibiotics

Linezolid & daptomycin

None

Antibiotics for gram positive coverage

Gram positive coverage with any of the above antibiotics

ICU admission

Mechanical ventilation

Patients in Modified Intent-To-Treat (MITT) analysis set.

Dr. Issam I Raad

Patients in MITT (Modified Intent-To-Treat) Analysis Set The MITT Analysis Set will be a subset of the ITT Analysis Set and will include all randomized patients who received any amount of inpatient IV study drug and meet minimal disease criteria (Inclusion Criterion 3). Patients will be analyzed according to randomized treatment group, regardless of treatment received.

Clinical Outcome in the MITT Analysis Set at EOIV.

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may continue on the study drug for up to 14 days. Patients may receive other addtional therapy.

Patients in mMITT (Microbiological Modified Intent-To-Treat) Analysis Set The mMITT Analysis Set will be a subset of the MITT Analysis Set and will include those patients for whom at least 1 qualifying bacterial pathogen was isolated from an appropriate microbiological specimen at baseline, irrespective of susceptibility to study therapies

Clinical Outcome in the mMITT Analysis Set at EOIV.

Patients in CE (Clinically Evaluable) Analysis Set - A subset of the MITT Analysis Set including patients with the following conditions:

Received \>=48 hrs of IV study drug to be considered an evaluable clinical failure, unless deemed a clinical failure based on a treatment-limiting AE Received \>=48 hrs of IV gram negative coverage to be considered an evaluable clinical cure Had clinical outcome assessment at TOC (other than indeterminate) or assessed as clinical failure at EOIV or TOC

Clinical Outcome in the CE Analysis Set at EOIV.

Pateints in MITT (Modified Intent-To-Treat) Analysis Set The MITT Analysis Set will be a subset of the ITT Analysis Set and will include all randomized patients who received any amount of inpatient IV study drug and meet minimal disease criteria (Inclusion Criterion 3). Patients will be analyzed according to randomized treatment group, regardless of treatment received.

Clinical Outcome in the MITT Analysis Set at TOC.

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may continue on the study drug for up to 14 days. Patients may receive other additional therapy.

Clinical Outcome in the MITT Analysis Set at LFU.

Patients in mMITT (Microbiological Modified Intent-To-Treat) Analysis Set The mMITT Analysis Set will be a subset of the MITT Analysis Set and will include those patients for whom at least 1 qualifying bacterial pathogen was isolated from an appropriate microbiological specimen at baseline, irrespective of susceptibility to study therapies.

Clinical Outcome in the mMITT Analysis Set at TOC.

Clinical Outcome in the mMITT Analysis Set at LFU.

Clinical Outcome in the CE Analysis Set at TOC.

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Patients may continue on the study drug for up to 14 days. Patients may receive other addtional therapy.

Clinical Outcome in the CE Analysis Set at LFU.

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other addtional therapy.

Patients in ME (Microbiologically Evaluable) Analysis Set The ME Analysis Set will include patients who meet the criteria for both the CE and mMITT analysis sets.

Clinical Outcome in the ME Analysis Set at EOIV.

Clinical Outcome in the ME Analysis Set at TOC.

Clinical Outcome in the ME Analysis Set at LFU.

Microbiological Outcome in the mMITT Analysis Set at EOIV.

Microbiological Outcome in the mMITT Analysis Set at TOC.

Microbiological Outcome in the mMITT Analysis Set at LFU.

Microbiological Outcome in the ME Analysis Set at EOIV.

Patients receive imipenem/cilastatin/relebactam IV over 30-60 minutes once every 6 hours (q6h) for 2 days for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or Patients may continue on the study drug for up to 14 days. Patients may receive other additional therapy..

Microbiological Outcome in the ME Analysis Set at TOC.

Microbiological Outcome in the ME Analysis Set at LFU.

Participants in MITT (Modified Intent-To-Treat) Analysis Set The MITT Analysis Set will be a subset of the ITT Analysis Set and will include all randomized patients who received any amount of inpatient IV study drug and meet minimal disease criteria (Inclusion Criterion 3). Patients will be analyzed according to randomized treatment group, regardless of treatment received.

Infection-related Mortality in the MITT Analysis Set at TOC.

Infection-related Mortality in the MITT Analysis Set at LFU.

Participants receive cefepime IV q8h for a minimum of 6 doses, or meropenem IV q8h for a minimum of 6 doses, or piperacillin/tazobactam IV q6h for a minimum of 8 doses. May also receive gram-positive therapy consisting of vancomycin IV q 12h or linezolid IV or orally (PO) q12h. Daptomycion could be given if no pneumonia. Participants may receive other additional therapy.

Infection-related Mortality in the mMITT Analysis Set at TOC.

Infection-related Mortality in the mMITT Analysis Set at LFU.

30-Day All-cause Mortality in the MITT Analysis Set.

Patients in MITT (Modified Intent-To-Treat) Analysis Set The mMITT Analysis Set will be a subset of the MITT Analysis Set and will include those patients for whom at least 1 qualifying bacterial pathogen was isolated from an appropriate microbiological specimen at baseline, irrespective of susceptibility to study therapies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN	NCT04983901	Hematopoietic a... Malignant Solid...	Imipenem/Cilast... Cefepime Meropenem Piperacillin-Ta... Vancomycin Daptomycin Linezolid	18 Years -	M.D. Anderson Cancer Center
Treatment of Neutropenic Patients With Fever Who Are Suspected to Have A Gram Positive Infection	NCT00035425	Febrile Neutrop...	linezolid vancomycin	13 Years -	Pfizer
PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN	NCT04983901	Hematopoietic a... Malignant Solid...	Imipenem/Cilast... Cefepime Meropenem Piperacillin-Ta... Vancomycin Daptomycin Linezolid	18 Years -	M.D. Anderson Cancer Center
PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN	NCT04983901	Hematopoietic a... Malignant Solid...	Imipenem/Cilast... Cefepime Meropenem Piperacillin-Ta... Vancomycin Daptomycin Linezolid	18 Years -	M.D. Anderson Cancer Center
PHASE II SINGLE-CENTER, RANDOMIZED, OPEN-LABEL, PROSPECTIVE, STUDY TO DETERMINE THE IMPACT OF SERIAL PROCALCITONIN	NCT04983901	Hematopoietic a... Malignant Solid...	Imipenem/Cilast... Cefepime Meropenem Piperacillin-Ta... Vancomycin Daptomycin Linezolid	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for linezolid

Every month we try and update this database with for linezolid cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for linezolid

Every month we try and update this database with for linezolid cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for linezolid cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.