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

Neutropenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05537896
• Other study ID #: 2206591296
• Status: Recruiting
• Phase: Phase 2
• Start date: February 19, 2024
• Est. completion date: February 2028

Study information

• Verified date: April 2024
• Source: West Virginia University
• Contact: Aaron Cumpston, PharmD, BCOP
• Phone: 3045984000
• Email: cumpstona[@]wvumedicine.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: February 2028
• Est. primary completion date: February 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancy
• Neoplasms
• Neutropenia

Intervention

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)

Locations

Country	Name	City	State
United States	Aaron Cumpston	Morgantown	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
West Virginia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Documented Breakthrough Infections	Number of Incidences documented that subjects had a confirmed breakthrough infection.	Up to 21 days
Secondary	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
Secondary	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
Secondary	All-cause mortality	Incidence of All-cause mortality defined as any death occurring during the clinical trial period.	Up to 30 days
Secondary	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
Secondary	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
Secondary	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