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

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ClinicalTrials.gov Identifier: NCT04983901
Recruitment Status : Recruiting
First Posted : July 30, 2021
Last Update Posted : July 26, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Hematopoietic and Lymphoid Cell Neoplasm Malignant Solid Neoplasm Drug: Cefepime Drug: Imipenem/cilastatin-relebactam Drug: Daptomycin Drug: Linezolid Drug: Meropenem Drug: Piperacillin-Tazobactam Drug: Vancomycin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Investigator Initiated, Phase IV 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 - Relebactam Plus Vancomycin or Linezolid Versus Standard of Care Antipseudomonal Beta-Lactams Plus Vancomycin or Linezolid as Empiric Therapy in Febrile Neutropenic Adults With Cancer
Actual Study Start Date : September 14, 2021
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group I (imipenem, cilastatin, relebactam)
Patients receive imipenem IV, cilastatin IV, and 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 IV, cilastatin IV, and relebactam IV over 30-60 minutes for up to 14 days if clinically indicated by the assessment of the treating physician.
Drug: Imipenem/cilastatin-relebactam
Given IV
Other Name: RECARBRIO™

Drug: Daptomycin
Given IV
Other Names:
  • Cubicin
  • LY146032

Drug: Linezolid
Given IV or PO
Other Name: Zyvox

Drug: Vancomycin
Given IV

Active Comparator: Group II (cefepime, meropenem, piperacillin/tazobactam)
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.
Drug: Cefepime
Given IV

Drug: Daptomycin
Given IV
Other Names:
  • Cubicin
  • LY146032

Drug: Linezolid
Given IV or PO
Other Name: Zyvox

Drug: Meropenem
Given IV
Other Names:
  • Meropenem Trihydrate
  • Merrem I.V.
  • SM-7338

Drug: Piperacillin-Tazobactam
Given IV
Other Names:
  • PIPER/TAZO
  • Piperacillin/Tazobactam
  • Zosyn

Drug: Vancomycin
Given IV




Primary Outcome Measures :
  1. Clinical response [ Time Frame: Up to 42 days ]
    The investigator will consider the entirety of the patient's clinical course and current status, including an evaluation of infection signs and symptoms (eg, fever, neutropenia), radiological findings (if applicable), and physical examination in order to classify the patient's clinical response at end of inpatient intravenous therapy (EOIV). The investigator could rely on physical exam performed by a professionally trained physician or health professional licensed to perform physical examinations. The investigator will use the serial procalcitonin (PCT) levels drawn at baseline and at 48-72 hours as an adjunct to the clinical judgement to guide antibiotic therapy and prevent unnecessary prolonged therapy with broad spectrum agents (imipenem/relebactam & standard of care [SOC]).

  2. Incidence of adverse events [ Time Frame: Up to 42 days ]
    Treatment-emergent adverse event (TEAEs), serious adverse events (SAEs), deaths, and discontinuations due to AEs will be summarized by treatment group, system organ class and preferred term according to the Medical Dictionary for Regulatory Activities, type, frequency, relationship to study therapy, and severity. Safety summaries will be presented using the Safety Analysis Set, according to the treatment actually received. Descriptive statistics of observed results and the change from baseline will be presented for clinical laboratory results and vital signs. The incidence of potentially clinically significant (PCS) laboratory results will be summarized. A list of all TEAEs/SAEs that resulted in deaths will also be generated. The changes in clinical laboratory parameters and vital sign parameters in the Safety Analysis Set at each study visit that assessments will be performed.


Secondary Outcome Measures :
  1. Clinical response [ Time Frame: Up to 42 days ]
    The investigator's assessment of clinical response at EOIV, time of clinical response (TOC), and late follow-up (LFU) will be used to determine the secondary clinical efficacy endpoints.

  2. Microbiological response [ Time Frame: Up to 42 days ]
    A patient's microbiological response at EOIV, TOC, and LFU will be determined programmatically based on individual outcomes for each baseline pathogen.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has provided written informed consent, and has the willingness and ability to comply with all study procedures
  • >= 18 years old
  • 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:

    • Absolute neutrophil count (ANC) < 500 cells/mm3 or has an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry and fever defined as:

      • 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 or urine pregnancy test within 5 days
    • 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 up 28 days post treatment

Exclusion Criteria:

  • History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic or carbapenem
  • 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)
  • Evidence of significant hepatic impairment (any of the following):

    • Known acute viral hepatitis
    • Alanine aminotransferase (ALT) level > 5 times the upper limit of normal (x upper limit of normal [ULN]). 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
  • 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 imipenem-relebactam trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04983901


Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Issam I. Raad    713-792-6237    iraad@mdanderson.org   
Principal Investigator: Issam I. Raad         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme LLC
Investigators
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Principal Investigator: Issam I Raad M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04983901    
Other Study ID Numbers: 2020-0074
NCI-2021-01957 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0074 ( Other Identifier: M D Anderson Cancer Center )
First Posted: July 30, 2021    Key Record Dates
Last Update Posted: July 26, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neoplasms
Vancomycin
Meropenem
Tazobactam
Linezolid
Piperacillin
Daptomycin
Imipenem
Cefepime
Piperacillin, Tazobactam Drug Combination
Relebactam
Cilastatin
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Synthesis Inhibitors
Protease Inhibitors