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

NCT04983901 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2020-0074NCI-2021-01957
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Clinical Outcome in the MITT Analysis Set at EOIV.

  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.

  Within 72 hours after administration of the last dose of inpatient IV study drug.

Secondary Outcomes (23)

• Clinical Outcome in the mMITT Analysis Set at EOIV.

  Within 72 hours after administration of the last dose of inpatient IV study drug.

• Clinical Outcome in the CE Analysis Set at EOIV.

  Within 72 hours after administration of the last dose of inpatient IV study drug.

• Clinical Outcome in the MITT Analysis Set at TOC.

  21 to 28 days after the start of inpatient IV study drug.

• Clinical Outcome in the MITT Analysis Set at LFU.

  35 to 42 days after the start of inpatient IV study drug.

• Clinical Outcome in the mMITT Analysis Set at TOC.

  21 to 28 days after the start of inpatient IV study drug.

Study Arms (2)

Group I (imipenem, cilastatin, relebactam)

EXPERIMENTAL

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.

Drug: Imipenem/Cilastatin/Relebactam; Drug: Vancomycin; Drug: Daptomycin; Drug: Linezolid

Group II (cefepime, meropenem, piperacillin/tazobactam)

ACTIVE COMPARATOR

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; Drug: Meropenem; Drug: Piperacillin-Tazobactam; Drug: Vancomycin; Drug: Daptomycin; Drug: Linezolid

Interventions

Imipenem/Cilastatin/Relebactam DRUG

Given IV

Also known as: RECARBRIO™

Group I (imipenem, cilastatin, relebactam)

Cefepime DRUG

Given IV

Group II (cefepime, meropenem, piperacillin/tazobactam)

Meropenem DRUG

Given IV

Also known as: Meropenem Trihydrate, Merrem I.V., SM-7338

Group II (cefepime, meropenem, piperacillin/tazobactam)

Piperacillin-Tazobactam DRUG

Given IV

Also known as: PIPER/TAZO, Piperacillin/Tazobactam, Zosyn

Group II (cefepime, meropenem, piperacillin/tazobactam)

Vancomycin DRUG

Given IV

Group I (imipenem, cilastatin, relebactam); Group II (cefepime, meropenem, piperacillin/tazobactam)

Daptomycin DRUG

Given IV

Also known as: Cubicin, LY146032

Group I (imipenem, cilastatin, relebactam); Group II (cefepime, meropenem, piperacillin/tazobactam)

Linezolid DRUG

Given IV or PO

Also known as: Zyvox

Group I (imipenem, cilastatin, relebactam); Group II (cefepime, meropenem, piperacillin/tazobactam)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \> 100.4 degree F (38.0 degree C).
• 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

You may not qualify if:

• History of any hypersensitivity or allergic reaction to any 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 \> 36 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Dagher H, Chaftari AM, Hachem R, Jiang Y, Philip A, Mulanovich P, Haddad A, Lamie P, Wilson Dib R, John TM, Dailey Garnes NJM, Ali S, Chaftari P, Raad II. Procalcitonin Level Monitoring in Antibiotic De-Escalation and Stewardship Program for Patients with Cancer and Febrile Neutropenia. Cancers (Basel). 2024 Oct 11;16(20):3450. doi: 10.3390/cancers16203450.

  PMID: 39456544 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

imipenem, cilastatin and relebactam; Cefepime; Meropenem; Piperacillin, Tazobactam Drug Combination; Vancomycin; Daptomycin; Linezolid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems; Tazobactam; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfones; Drug Combinations; Pharmaceutical Preparations; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Issam I Raad
• Organization: The University of M.D. Anderson Cancer Center

iraad@mdanderson.org

713-792-6237

Study Officials

• Issam I Raad

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: July 30, 2021
• Study Start: September 14, 2021
• Primary Completion: October 6, 2023
• Study Completion: October 6, 2023
• Last Updated: November 4, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-07

Locations

US (1)