Back to results

Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients

Primary Purpose

Hematopoietic and Lymphoid Cell Neoplasm, Influenza

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Baloxavir Marboxil

Oseltamivir

About this trial

This is an interventional treatment trial for Hematopoietic and Lymphoid Cell Neoplasm

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Hematopoeitic cell transplant recipients OR hematological malignancy patients
Diagnosed with influenza ⱡ
Evidence of LRTI* or high risk upper respiratory tract infection (URTI)**

ⱡ A positive multiplex PCR for influenza is required to confirm a diagnosis of influenza infection.

* LRTI will be defined as influenza cases that have evidence of disease below the level of the trachea on either imaging only (possible LRTI), imaging and microbiological evidence of lower airway disease with a bronchoscopy (probable LRTD) or pathological evidence of disease via biopsy (proven LRTI).

** High risk URI will be defined as those cases of influenza that do not have microbiological nor radiological evidence of LRTI, yet they have an immunodeficiency scoring index (ISI) of 3 or greater as defined by Shah D et al (19) for HCT recipients or severe neutropenia (ANC ≤500 cells/ml) and/or lymphopenia (ALC ≤200 cells/ml) for HM patients.

Exclusion criteria:

Patient requires mechanical ventilation at time of enrollment
Patient is younger than the age of 12 years old
The patient is unable to tolerate oral therapy
The patient is pregnant at screening ( Positive serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential).
The patient is on a prohibited medication. These include Influenza antiviral drugs with the exception of oseltamivir and baloxavir (such as peramivir, laninamivir, zanamivir, rimantadine, umifenovir or amantadine) and herbal therapies.
The patient is unable to consent will be excluded

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (oseltamivir, baloxavir marboxil)

Arm II (oseltamivir)

Arm Description

Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Changes in viral loads

Will be measured via repeat nasopharyngeal swabs at each follow up on day 0, 1, 3, 7, 14 and 30 for influenza quantification.

Incidence of complicated hospital stay

Defined as a hospital admission that was either prolonged (greater than 7 days), requiring intensive care unit level of care or death at day 30 as a result of influenza infection.

Secondary Outcome Measures

Rate of resistance to antiviral agents

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Progression to lower respiratory tract infections

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Length of hospital stay

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Oxygen requirement

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Rate of respiratory failure

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

30-day mortality

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Changes in microbiome diversity

Analysis of alpha and beta diversity of microbiome will be assessed using Agile Toolkit for Incisive Microbial Analyses. Using Shannon index, we will quantify the alpha diversity of the microbiome. Changes in microbiome diversity will be made by comparing alpha diversity at each time point of sample collection (days 0, 1, 3, 7, 14 and 30).

Full Information

NCT ID

NCT04712539

First Posted

January 13, 2021

Last Updated

October 5, 2023

Sponsor

M.D. Anderson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT04712539

Brief Title

Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients

Official Title

Efficacy of Combination Baloxovir and Oseltamivir Therapy in Influenza Infected Immunocompromised Hosts

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 11, 2021 (Actual)

Primary Completion Date

February 28, 2024 (Anticipated)

Study Completion Date

February 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase II trial studies the effect of baloxavir in combination with oseltamivir in treating severe influenza infection in patients who have previously received a hematopoietic (blood) stem cell transplant or have a hematological malignancy. Baloxavir is an antiviral drug that inhibits the growth of influenza virus, reduces viral load and prevents further influenza infection. Osetamivir is an antiviral drug that blocks enzymes on the surfaces of influenza viruses, interfering with cell release of complete viral particles. Giving baloxavir in combination with oseltamivir may shorten or decrease the intensity of influenza infection compared to oseltamivir alone.

Detailed Description

PRIMARY OBJECTIVE: I. To compare the efficacy of baloxavir marboxil (baloxavir) in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 1 from baseline for treatment of severe influenza infections in immunocompromised hosts (such as hematopoietic cell transplant [HCT] recipients and hematological malignancy [HM] patients) and compare the main clinical outcome, complicated hospital stay between the intervention arm and control arm. SECONDARY OBJECTIVES: I. To compare the efficacy of baloxavir in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 3, 7, 14 and 30 from baseline. II. To measure the incidence of baloxavir and oseltamivir resistance, development of lower respiratory tract infections (LRTI), oxygen requirement, respiratory failure, changes in microbiome of the upper airway, length of hospital stay and all-cause mortality at day 30 while on baloxavir and/or oseltamivir in these immunocompromised hosts. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive oseltamivir orally (PO) twice daily (BID) for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up at 30 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematopoietic and Lymphoid Cell Neoplasm, Influenza

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I (oseltamivir, baloxavir marboxil)

Arm Type

Experimental

Arm Description

Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Arm Title

Arm II (oseltamivir)

Arm Type

Active Comparator

Arm Description

Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

Baloxavir Marboxil

Other Intervention Name(s)

BXM, Xofluza

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

Oseltamivir

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Changes in viral loads

Description

Will be measured via repeat nasopharyngeal swabs at each follow up on day 0, 1, 3, 7, 14 and 30 for influenza quantification.

Time Frame

On day 0, 1, 3, 7, 14, and 30

Title

Incidence of complicated hospital stay

Description

Defined as a hospital admission that was either prolonged (greater than 7 days), requiring intensive care unit level of care or death at day 30 as a result of influenza infection.

Time Frame

Up to 30 days

Secondary Outcome Measure Information:

Title

Rate of resistance to antiviral agents

Description

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Time Frame

Up to 30 days

Title

Progression to lower respiratory tract infections

Description

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Time Frame

Up to 30 days

Title

Length of hospital stay

Description

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Time Frame

Up to 30 days

Title

Oxygen requirement

Description

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Time Frame

Up to 30 days

Title

Rate of respiratory failure

Description

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Time Frame

Up to 30 days

Title

30-day mortality

Description

Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Time Frame

At 30 days

Title

Changes in microbiome diversity

Description

Time Frame

On day 0, 1, 3, 7, 14, and 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Hematopoeitic cell transplant recipients OR hematological malignancy patients Diagnosed with influenza ⱡ Evidence of LRTI* or high risk upper respiratory tract infection (URTI)** ⱡ A positive multiplex PCR for influenza is required to confirm a diagnosis of influenza infection. * LRTI will be defined as influenza cases that have evidence of disease below the level of the trachea on either imaging only (possible LRTI), imaging and microbiological evidence of lower airway disease with a bronchoscopy (probable LRTD) or pathological evidence of disease via biopsy (proven LRTI). ** High risk URI will be defined as those cases of influenza that do not have microbiological nor radiological evidence of LRTI, yet they have an immunodeficiency scoring index (ISI) of 3 or greater as defined by Shah D et al (19) for HCT recipients or severe neutropenia (ANC ≤500 cells/ml) and/or lymphopenia (ALC ≤200 cells/ml) for HM patients. Exclusion criteria: Patient requires mechanical ventilation at time of enrollment Patient is younger than the age of 12 years old The patient is unable to tolerate oral therapy The patient is pregnant at screening ( Positive serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential). The patient is on a prohibited medication. These include Influenza antiviral drugs with the exception of oseltamivir and baloxavir (such as peramivir, laninamivir, zanamivir, rimantadine, umifenovir or amantadine) and herbal therapies. The patient is unable to consent will be excluded

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Roy F. Chemaly, MD,MPH

Phone

713-792-6830

rfchemaly@mdanderson.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roy F Chemaly, MD,MPH

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Roy F. Chemaly, MD,MPH

Phone

713-792-6830

rfchemaly@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Roy F. Chemaly, MD,MPH

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center

Learn more about this trial

Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients

We'll reach out to this number within 24 hrs