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

Malignant Solid Neoplasm Clinical Trial

Official title: 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

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Neoplasms

• NCT number: NCT04983901
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 2
• Start date: September 14, 2021
• Completion date: October 6, 2023