Prospective Evaluation of Xerava Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia

Prospective Evaluation of Xerava™ (Eravacycline) Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia

Antibacterial prophylaxis is recommended in patients at high risk of infection, specifically patients undergoing acute leukemia induction therapy or hematopoietic stem cell transplant (HSCT) who are expected to have profound neutropenia (ANC<100 neutrophils/milliliter) for more than seven days. Xerava™ (eravacycline) has a broad spectrum of activity including many multi-drug resistant strains of bacteria. It is not an agent used for treatment of febrile neutropenia, making eravacycline a very attractive alternative to consider in this prophylactic setting. Eravacycline has activity against MRSA, VRE, and Clostridioides difficile, all of which are common problems in this patient population. It also covers the majority of enteric gram-negative pathogens while also producing satisfactory tissue penetration and adequate plasma concentrations, which has classically been a concern with prior agents. Eravacycline has activity against coagulase-negative staphylococcus, which is a common catheter-related infection in leukemia and HSCT patients. The primary objective will be report the incidence of breakthrough infections during eravacycline prophylaxis for hematologic malignancy patients with prolonged neutropenia.

Study Overview

• Status: Recruiting
• Conditions: Neutropenia; Hematological Malignancy
• Intervention / Treatment: Drug: Eravacycline

Detailed Description

Antibacterial prophylaxis is recommended in patients at high risk of infection, specifically patients undergoing acute leukemia induction therapy or hematopoietic stem cell transplant (HSCT) who are expected to have profound neutropenia (ANC<100 neutrophils/milliliter) for more than seven days.

Xerava™ (eravacycline) is a synthetic halogenated tetracycline class antibiotic, with a broad spectrum of activity including many multi-drug resistant strains of bacteria. It is not an agent used for treatment of febrile neutropenia, making eravacycline a very attractive alternative to consider in this prophylactic setting. Adverse effects with this agent are minimal including infusion site reactions and gastrointestinal disorders. Eravacycline has activity against MRSA, VRE, and Clostridioides difficile, all of which are common problems in this patient population. It also covers the majority of enteric gram-negative pathogens while also producing satisfactory tissue penetration and adequate plasma concentrations, which has classically been a concern with prior agents. Eravacycline has activity against coagulase-negative staphylococcus, which is a common catheter-related infection in leukemia and HSCT patients. The primary objective will be report the incidence of breakthrough infections during eravacycline prophylaxis for hematologic malignancy patients with prolonged neutropenia.

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aaron Cumpston, PharmD, BCOP; Phone Number: 73350 3045984000; Email: cumpstona@wvumedicine.org

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • Aaron Cumpston
      • Contact: Aaron Cumpston, PharmD, BCOP; Phone Number: 3045984000; Email: cumpstona@wvumedicine.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients receiving induction chemotherapy for treatment of acute leukemia or receiving preparative regimen for HSCT
• Patient must provide informed consent.
• Bilirubin ≤ 3 x the ULN and AST/ALT ≤ 5 x ULN

Exclusion Criteria:

• Uncontrolled bacterial, viral or fungal infection at the time of study enrollment.
• Urinary tract infection receiving active treatment
• Acute pancreatitis (not necessary to work-up unless symptomatic)
• History of known hypersensitivity to eravacycline, tetracycline, doxycycline, minocycline, tigecycline, sarecycline, oxytetracycline, or omadacycline
• Pseudomonas infection within 30 days prior to study enrollment
• Receiving strong inhibitors or inducers of cytochrome P450 3A4 will be excluded from the study (see Appendix B for complete list of medications)
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eravacycline; Eravacycline- 1 mg/kg actual body weight IV Infusion over 60 minutes every 12 hours. Alternative dosing strategy 1.5mg/kg every 12 hourse.	Drug: Eravacycline; Eravacycline will be continued until one of the following criteria is met: neutrophil recovery (ANC >500, post-nadir); febrile neutropenia; breakthrough infection; any grade 3-4 toxicity related to eravacycline use; 21 days of therapy (maximum duration allowed per study protocol); Other Names: Xerava

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Documented Breakthrough Infections	Number of Incidences documented that subjects had a confirmed breakthrough infection.	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence of Adverse Events: CTCAE criteria. CTCAE stands for Common Terminology Criteria for Adverse Events; these criteria are also called "common toxicity criteria." In CTCAE, an adverse event (AE) is defined as any abnormal clinical finding temporally associated with the use of a therapy for cancer; causality is not required. These criteria are used for the management of chemotherapy administration and dosing, and in clinical trials to provide standardization and consistency in the definition of treatment-related toxicity.	Daily during Eravacycline
Infection-related mortality	Incidence of Infection-related mortality. Infection-related mortality is defined as any death that occurred in the presence of clinical or microbiological documented infection	Up to 30 days
All-cause mortality	Incidence of All-cause mortality defined as any death occurring during the clinical trial period.	Up to 30 days
Acute GVHD	Incidence of Acute Graft vs Host Disease (GVHD). GVHD is a complication of a bone marrow or stem cell transplant in which cells from a donor attack the tissues of the recipient.	Up to 100 days
Time to neutropenic fever	Time to development of febrile neutropenia (temperature >38.2 degrees C and ANC is <500 cells/mm3).	Up to 21 days
Neutropenic fever	Rate of neutropenic fever: Defined as development of febrile neutropenia (temperature >38.2 degrees C and ANC is <500 cells/mm3).	Up to 21 days

Collaborators and Investigators

• Sponsor: West Virginia University
• Investigators: Principal Investigator: Aaron Cumpston, PharmD, BCOP, West Virginia University

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Neoplasms by Site; Neoplasms; Leukocyte Disorders; Hematologic Diseases; Leukopenia; Agranulocytosis; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Neutropenia; eravacycline
• Other Study ID Numbers: 2206591296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No