Eravacycline Prophylaxis for Blood Cancers

Overseen By Aaron Cumpston, PharmD, BCOP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: West Virginia University

Must not be taking: Cytochrome P450 3A4

Disqualifiers: Uncontrolled infection, Pancreatitis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking strong inhibitors or inducers of cytochrome P450 3A4. Check Appendix B for a list of these medications.

How is the drug Eravacycline unique for blood cancer patients?

Eravacycline is unique because it is a newer antibiotic that can be used to prevent infections in blood cancer patients, particularly those who might be at risk for infections like vancomycin-resistant enterococci (VRE), which are difficult to treat with standard antibiotics. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Aaron Cumpston, PharmD, BCOP

Principal Investigator

West Virginia University

Eligibility Criteria

This trial is for patients with blood cancers undergoing acute leukemia therapy or stem cell transplant, expected to have very low white blood cells for over a week. They must understand the study and agree to participate, have certain liver function test levels within set limits, and not be pregnant or breastfeeding.

Inclusion Criteria

I am undergoing chemotherapy for acute leukemia or preparing for a stem cell transplant.

Patient must provide informed consent

Bilirubin ≤ 3 x the ULN and AST/ALT ≤ 5 x ULN

Exclusion Criteria

I am currently being treated for a urinary tract infection.

I am not taking any strong medication that affects liver enzymes.

Pregnant or lactating women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Eravacycline prophylaxis for hematologic malignancy patients with prolonged neutropenia

21 days

Daily visits for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term follow-up

Participants are monitored for long-term outcomes such as infection-related mortality and acute GVHD

100 days

Treatment Details

Interventions

• Eravacycline

Trial Overview The trial tests Xerava™ (eravacycline) as a preventive antibiotic in patients at high risk of infection due to prolonged neutropenia from leukemia treatment or stem cell transplant. The goal is to see if it can prevent infections better than current treatments.

Participant Groups

Group I: Eravacycline Experimental Treatment 1 Intervention

Eravacycline- 1 mg/kg actual body weight IV Infusion over 60 minutes every 12 hours. Alternative dosing strategy 1.5mg/kg every 12 hourse.

Eravacycline is already approved in United States for the following indications:

Approved in United States as Xerava for:

• Complicated intra-abdominal infections

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Findings from Research

In a study involving 56 oncology patients with vancomycin-resistant enterococci (VRE) infections, the combination of quinopristin-dalfopristin and minocycline showed a response rate of 68%, indicating its effectiveness against these infections.

The treatment was associated with a notable side effect, with 36% of patients experiencing arthralgia or myalgia, highlighting the need to consider potential adverse effects when using this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline. Raad, I., Hachem, R., Hanna, H., et al.[2018]

In a study of 197 cancer patients, 13.4% developed bloodstream infections from vancomycin-resistant Enterococcus faecium (VRE), highlighting the serious risk of VRE infections in this population.

Key risk factors for developing VRE bloodstream infections included the use of vancomycin, diabetes, gastrointestinal procedures, and acute renal failure, suggesting that limiting vancomycin use and gastrointestinal interventions could help prevent these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci. Zaas, AK., Song, X., Tucker, P., et al.[2007]

In a study of allogeneic hematopoietic cell transplantation patients, VRE bacteremia (VREB) was found to be infrequent, indicating a low incidence of this infection in the cohort.

Colonized patients were more likely to receive VRE-directed therapy compared to noncolonized patients, suggesting that screening for VRE may influence treatment decisions even in the absence of active infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unintended Consequences of Pretransplant Vancomycin-Resistant Enterococcus Screening on Antimicrobial Stewardship Among Allogeneic Hematopoietic Cell Transplant Recipients. Stohs, EJ., MacAllister, T., Pergam, SA., et al.[2019]

In a study of 434 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, empiric therapy for vancomycin-resistant Enterococcus (VRE) bacteremia did not show a significant benefit compared to directed therapy, with similar clinical outcomes such as duration of bacteremia and mortality rates.

The findings suggest that empiric use of VRE-active agents in febrile, neutropenic patients who are VRE-colonized is not recommended, as it did not improve survival or reduce complications compared to targeted treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Empiric Treatment for Vancomycin-Resistant Enterococcus in Colonized Patients Early after Allogeneic Hematopoietic Stem Cell Transplantation. Kamboj, M., Cohen, N., Huang, YT., et al.[2020]

In a study of 56 neutropenic cancer patients colonized with vancomycin-resistant enterococci (VRE), those with acute leukemia were significantly more likely to develop VRE bacteremia, with 100% of affected patients having acute leukemia compared to 56% of those without bacteremia.

C. difficile infection was identified as a major risk factor for developing VRE bacteremia, with a risk ratio of 8.2, highlighting the importance of monitoring for C. difficile in VRE-colonized patients, especially those with acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clostridium difficile infection is a risk factor for bacteremia due to vancomycin-resistant enterococci (VRE) in VRE-colonized patients with acute leukemia. Roghmann, MC., McCarter, RJ., Brewrink, J., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci. [2007]

3. United States pubmed.ncbi.nlm.nih.gov

Unintended Consequences of Pretransplant Vancomycin-Resistant Enterococcus Screening on Antimicrobial Stewardship Among Allogeneic Hematopoietic Cell Transplant Recipients. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of Empiric Treatment for Vancomycin-Resistant Enterococcus in Colonized Patients Early after Allogeneic Hematopoietic Stem Cell Transplantation. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Clostridium difficile infection is a risk factor for bacteremia due to vancomycin-resistant enterococci (VRE) in VRE-colonized patients with acute leukemia. [2020]