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

Phase 2

Recruiting

• Conditions: Hematological Malignancy; Neutropenia
• Interventions: Drug: Eravacycline

• Registration Number: NCT05537896
• Lead Sponsor: West Virginia University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-09-12
• Study First Submitted QC: 2022-09-12
• Study First Posted: 2022-09-13
• Study Start: 2024-02-19
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-11
• Primary Completion: 2028-02
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 55

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eravacycline	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Documented Breakthrough Infections	Up to 21 days	Number of Incidences documented that subjects had a confirmed breakthrough infection.

Secondary Outcome Measures

Name	Time	Method
Acute GVHD	Up to 100 days	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.
Time to neutropenic fever	Up to 21 days	Time to development of febrile neutropenia (temperature \>38.2 degrees C and ANC is \<500 cells/mm3).
Neutropenic fever	Up to 21 days	Rate of neutropenic fever: Defined as development of febrile neutropenia (temperature \>38.2 degrees C and ANC is \<500 cells/mm3).
Adverse Events	Daily during Eravacycline	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.
Infection-related mortality	Up to 30 days	Incidence of Infection-related mortality. Infection-related mortality is defined as any death that occurred in the presence of clinical or microbiological documented infection
All-cause mortality	Up to 30 days	Incidence of All-cause mortality defined as any death occurring during the clinical trial period.

Trial Locations

Locations (1)

Aaron Cumpston; 🇺🇸 Morgantown, West Virginia, United States