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

Study Overview
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Brief Summary
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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 antibiotic prophylaxis failure with eravacycline prophylaxis for hematologic malignancy patients with prolonged neutropenia.

Detailed Description
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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 antibiotic prophylaxis failure with eravacycline prophylaxis for hematologic malignancy patients with prolonged neutropenia.

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

Conditions
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Hematological Malignancy, Neutropenia

Intervention / Treatment
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* Drug: Eravacycline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xerava<br>Eravacycline- 1 mg/kg actual body weight IV Infusion over 60 minutes every 12 hours | Drug: Eravacycline<br>* 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<br>* Other names: Xerava;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibiotic Prophylaxis Failure-Incidence | Incidence of antibiotic failure--Antibiotic prophylaxis failure is defined as development of febrile neutropenia (temperature >38.2 degrees C and ANC is <500 cells/mm3). | Up to 114 days | 
| Antibiotic Prophylaxis Failure- Time | Time to failure--Antibiotic prophylaxis failure is defined as development of febrile neutropenia (temperature >38.2 degrees C and ANC is <500 cells/mm3). | Up to 114 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 114 days | 
| All-cause mortality | Incidence of All-cause mortality defined as any death occurring during the clinical trial period. | Up to 114 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 114 days |