Clinical trial NCT05537896: Prospective Evaluation of Xerava Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia
Official title: Prospective Evaluation of Xerava™ (Eravacycline) Prophylaxis in Hematological Malignancy Patients With Prolonged Neutropenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hematological Malignancy
Neutropenia
Lead sponsor: West Virginia University
Sponsor class: OTHER
First posted: 2022-09-13
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Documented Breakthrough Infections
timeFrame: Up to 21 days
Secondary outcomes:
measure: Adverse Events
timeFrame: Daily during Eravacycline
measure: Infection-related mortality
timeFrame: Up to 30 days
measure: All-cause mortality
timeFrame: Up to 30 days
measure: Acute GVHD
timeFrame: Up to 100 days
measure: Neutropenic fever
timeFrame: Up to 21 days
measure: Time to neutropenic fever
timeFrame: Up to 21 days
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: Aaron Cumpston
state: West Virginia
Study officials:
affiliation: West Virginia University
name: Aaron Cumpston, PharmD, BCOP
role: PRINCIPAL_INVESTIGATOR
References: