Isavuconazole in Preventing Invasive Fungal Infections in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome and Neutropenia

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT03019939
Collaborator
National Cancer Institute (NCI) (NIH)
65
Enrollment
1
Location
1
Arm
40.4
Actual Duration (Months)
1.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well isavuconazole works in preventing invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndrome and neutropenia. Isavuconazole may help to prevent invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndrome and neutropenia.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess whether prophylaxis with isavuconazole effectively prevents the occurrence of proven or probable invasive fungal infections (IFIs) in patients with newly diagnosed acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) receiving successive cycles of intensive chemotherapy or other therapies for up to 100 days from prophylaxis initiation.
SECONDARY OBJECTIVES:
  1. To evaluate the incidence of invasive aspergillosis (IA) within 100 days of beginning isavuconazole prophylaxis in newly diagnosed patients with AML/MDS receiving intensive chemotherapy or other therapies.

  2. To evaluate the incidence of other IFIs within 100 days of beginning isavuconazole prophylaxis in newly diagnosed patients with AML/MDS receiving intensive chemotherapy or other therapies.

  3. To evaluate the composite outcome of treatment success versus (vs.) failure in this patient population.

  4. To measure the overall survival (OS) of study participants. V. To measure the IFI-free survival of study participants. VI. To document the time to death from any cause in the study population. VII. To document the time to death related to IFI in the study population. VIII. To document the time to diagnosis of proven or probable IFI in the study population.

  5. To document the time to initiation of empiric anti-fungal therapy in the study population.

  6. To characterize the safety, tolerability and adverse event (AE) profile of isavuconazole in the prophylactic setting.

EXPLORATORY OBJECTIVES:
  1. To assess the potential role, if any, of therapeutic drug monitoring (TDM) of isavuconazole levels in the prophylactic setting in patients with newly diagnosed AML/MDS receiving cytotoxic chemotherapy or other therapies.

  2. To determine the in vitro susceptibility of agents causing "breakthrough" IFIs to antifungal agents.

OUTLINE:

Patients receive isavuconazole orally (PO) every 8 hours for 6 doses and then once daily (QD) or intravenously (IV) over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity.

Study Design

Study Type:
Interventional
Actual Enrollment :
65 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
A Phase II Study of Isavuconazole Prophylaxis in Adult Patients With AML/MDS and Neutropenia
Actual Study Start Date :
Mar 28, 2017
Actual Primary Completion Date :
Aug 10, 2020
Actual Study Completion Date :
Aug 10, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Prevention (isavuconazole)

Patients receive isavuconazole PO every 8 hours for 6 doses and then Once a day (QD) or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Isavuconazole
Given PO or IV
Other Names:
  • BAL8557
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Proven or Probable Invasive Fungal Infections (IFIs) [Up to 100 days from prophylaxis initiation]

      Participants with proven or possible invasive fungal infections.

    Secondary Outcome Measures

    1. Number of Participants With Invasive Aspergillosis [Up to 100 days from prophylaxis initiation]

      Participants with invasive aspergillosissured.

    2. Number of Participants With Other Invasive Fungal Infections (IFIs) [Up to 100 days from prophylaxis initiation]

      Participants with other IFIs will be measured.

    3. Number of Participants With Treatment Success [Up to 3 years]

      Will evaluate versus (vs.) failure (defined as Participants with proven or probable IFI, receipt of any other systemic antifungal agent for +/- 4 days for suspected IFI, occurrence of an adverse events possibly or probably related to the study drug resulting in discontinuation of treatment, or withdrawal from the study with no additional follow-up).

    4. Number of Participants Who Failed Treatment [Up to 3 years]

      Will evaluate versus success. Success is defined as Participants with proven or probable IFI, receipt of any other systemic antifungal agent for +/- 4 days for suspected IFI, occurrence of an adverse events possibly or probably related to the study drug resulting in discontinuation of treatment, or withdrawal from the study with no additional follow-up).

    5. Overall Survival (OS) [Up to 3 years]

      Time from date of treatment start until date of death due to any cause or last Follow-up.

    6. Invasive Fungal Infections (IFIs)-Free Survival [Up to 3 years]

      Time measured in days from start of treatment to IFI or off study date

    7. Time to Death From Any Cause [Up to 3 years]

      Time to death from any cause will be measured.

    8. Number of Participants With Death Related to Invasive Fungal Infections (IFIs) [Up to 3 years]

      Death's from invasive fungal infections

    9. Time to Diagnosis of Proven or Probable Invasive Fungal Infections (IFIs) [Up to 3 years]

      Time measured in days from start of treatment to invasive fungal infections

    10. Time to Initiation of Empiric Anti-fungal Therapy [Up to 3 years]

      Time days from start of empiric anti-fungal therapy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with either newly diagnosed AML or MDS who have either begun (within 4 days of starting study drug) or are planned to begin specific treatment for their AML/MDS; hydroxyurea and cytarabine used for cytoreduction while awaiting initiation of definitive therapy are not considered "specific" treatment; patients who are participating in other therapeutic clinical trials for their AML/MDS may participate in this trial

    • Patients must have or be anticipated to have neutropenia (absolute neutrophil count [ANC] < 0.5 x 10^9/L) (75) for >= 7 days as a result of treatment of their AML/MDS

    • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

    • Total bilirubin =< 3 x upper limit of normal (ULN)

    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 x ULN

    • Patients must be able to take oral medications, although a brief period of IV therapy (< 4 days) is permitted at trial entry

    • Patients must be willing and able to provide written informed consent for the trial

    • Women of childbearing potential (WOCBP) must practice 2 effective methods of birth control during the course of the study; male patients who are partners of WOCBP should also practice an effective method of contraception; effective methods of birth control include diaphragm or condoms with spermicidal foam or jelly, birth control pills (BCPs), injections or patches, intra-uterine devices (IUDs) and surgical sterilization

    • Postmenopausal women must be amenorrheic for >= 12 months to be considered of non-childbearing potential

    • Women and men must continue birth control for the duration of the trial and >= 3 months after the last dose of study drug

    • All WOCBP MUST have a negative pregnancy test prior to first receiving study medication

    Exclusion Criteria:
    • Proven, probable or possible IFI within the previous 30 days

    • Use of any systemic antifungal therapy for > 72 hours during the week prior to study drug initiation

    • History of hypersensitivity or idiosyncratic reactions to azoles

    • Patients with familial short QT syndrome or with corrected QT (QTc) interval =< 300 ms

    • Patients on strong CYP3A4 inducers or inhibitors that cannot be discontinued

    • Women who are pregnant or nursing, or intend to be/do so during the course of the study

    • Patients with severe hepatic impairment (Child-Pugh class C)

    • Patients with known or suspected Gilbert's syndrome at the time of study enrollment

    • Patients with known gastrointestinal conditions that could potentially interfere with absorption of orally administered medications

    • Any condition that, in the opinion of the investigator, may interfere with the objectives of the study, e.g., any condition requiring the use of prohibited drugs or unstable medical conditions other than AML/MDS, such as a cardiac or neurologic disorder expected to be unstable or progressive during the course of the study (e.g., seizures or demyelinating syndromes, acute myocardial infarction within 3 months of study entry, myocardial ischemia or unstable congestive heart failure, unstable arrhythmias)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1M D Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Prithviraj Bose, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03019939
    Other Study ID Numbers:
    • 2016-0373
    • NCI-2017-00323
    • 2016-0373
    First Posted:
    Jan 13, 2017
    Last Update Posted:
    Oct 26, 2021
    Last Verified:
    Oct 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsRecruitment Period: April 28, 2017 to July 26, 2019
    Pre-assignment Detail
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Period Title: Overall Study
    STARTED65
    COMPLETED65
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Overall Participants65
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    31
    47.7%
    >=65 years
    34
    52.3%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    67
    Sex: Female, Male (Count of Participants)
    Female
    29
    44.6%
    Male
    36
    55.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    3
    4.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    3
    4.6%
    White
    57
    87.7%
    More than one race
    0
    0%
    Unknown or Not Reported
    2
    3.1%
    Region of Enrollment (participants) [Number]
    United States
    65
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants With Proven or Probable Invasive Fungal Infections (IFIs)
    DescriptionParticipants with proven or possible invasive fungal infections.
    Time FrameUp to 100 days from prophylaxis initiation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Count of Participants [Participants]
    4
    6.2%
    2. Secondary Outcome
    TitleNumber of Participants With Invasive Aspergillosis
    DescriptionParticipants with invasive aspergillosissured.
    Time FrameUp to 100 days from prophylaxis initiation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Count of Participants [Participants]
    2
    3.1%
    3. Secondary Outcome
    TitleNumber of Participants With Other Invasive Fungal Infections (IFIs)
    DescriptionParticipants with other IFIs will be measured.
    Time FrameUp to 100 days from prophylaxis initiation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Count of Participants [Participants]
    2
    3.1%
    4. Secondary Outcome
    TitleNumber of Participants With Treatment Success
    DescriptionWill evaluate versus (vs.) failure (defined as Participants with proven or probable IFI, receipt of any other systemic antifungal agent for +/- 4 days for suspected IFI, occurrence of an adverse events possibly or probably related to the study drug resulting in discontinuation of treatment, or withdrawal from the study with no additional follow-up).
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Count of Participants [Participants]
    46
    70.8%
    5. Secondary Outcome
    TitleNumber of Participants Who Failed Treatment
    DescriptionWill evaluate versus success. Success is defined as Participants with proven or probable IFI, receipt of any other systemic antifungal agent for +/- 4 days for suspected IFI, occurrence of an adverse events possibly or probably related to the study drug resulting in discontinuation of treatment, or withdrawal from the study with no additional follow-up).
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Count of Participants [Participants]
    19
    29.2%
    6. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionTime from date of treatment start until date of death due to any cause or last Follow-up.
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Median (Full Range) [Months]
    19.9
    7. Secondary Outcome
    TitleInvasive Fungal Infections (IFIs)-Free Survival
    DescriptionTime measured in days from start of treatment to IFI or off study date
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Median (Full Range) [Days]
    86
    8. Secondary Outcome
    TitleTime to Death From Any Cause
    DescriptionTime to death from any cause will be measured.
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Median (Full Range) [Months]
    4
    9. Secondary Outcome
    TitleNumber of Participants With Death Related to Invasive Fungal Infections (IFIs)
    DescriptionDeath's from invasive fungal infections
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Count of Participants [Participants]
    0
    0%
    10. Secondary Outcome
    TitleTime to Diagnosis of Proven or Probable Invasive Fungal Infections (IFIs)
    DescriptionTime measured in days from start of treatment to invasive fungal infections
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Median (Full Range) [Days]
    24
    11. Secondary Outcome
    TitleTime to Initiation of Empiric Anti-fungal Therapy
    DescriptionTime days from start of empiric anti-fungal therapy.
    Time FrameUp to 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    Measure Participants65
    Median (Full Range) [Days]
    22

    Adverse Events

    Time FrameUp to 3 years
    Adverse Event Reporting Description
    Arm/Group TitlePrevention (Isavuconazole)
    Arm/Group DescriptionPatients receive isavuconazole PO every 8 hours for 6 doses and then QD or IV over 1 hour every 8 hours for 6 doses and then QD for up to 4 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Isavuconazole: Given PO or IV
    All Cause Mortality
    Prevention (Isavuconazole)
    Affected / at Risk (%)# Events
    Total4/65 (6.2%)
    Serious Adverse Events
    Prevention (Isavuconazole)
    Affected / at Risk (%)# Events
    Total30/65 (46.2%)
    Blood and lymphatic system disorders
    Neutropenic Fever17/65 (26.2%) 19
    Cardiac disorders
    Supraventricular Tachycardia1/65 (1.5%) 1
    Gastrointestinal disorders
    Nausea1/65 (1.5%) 1
    General disorders
    Abdominal Pain1/65 (1.5%) 1
    Death1/65 (1.5%) 1
    Fever4/65 (6.2%) 5
    Pain Extremity1/65 (1.5%) 1
    Infections and infestations
    Infection2/65 (3.1%) 2
    Lung Infection1/65 (1.5%) 1
    Sepsis4/65 (6.2%) 4
    Skin Infection1/65 (1.5%) 1
    Upper Respiratory Infection1/65 (1.5%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia1/65 (1.5%) 2
    Renal and urinary disorders
    Acute Kidney Injury1/65 (1.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/65 (1.5%) 1
    Other (Not Including Serious) Adverse Events
    Prevention (Isavuconazole)
    Affected / at Risk (%)# Events
    Total14/65 (21.5%)
    Blood and lymphatic system disorders
    Neutropenic Fever7/65 (10.8%) 8
    Gastrointestinal disorders
    Colitis1/65 (1.5%) 1
    Gastrointestinal Other1/65 (1.5%) 1
    Oral Pain2/65 (3.1%) 2
    General disorders
    Fever2/65 (3.1%) 2
    Infections and infestations
    Infection1/65 (1.5%) 1
    Sinusitis1/65 (1.5%) 1
    Investigations
    Alanine Aminotransferase Increased3/65 (4.6%) 3
    Aspartate Aminotransferase Increased2/65 (3.1%) 2
    Metabolism and nutrition disorders
    Tumor Lysis Syndrome1/65 (1.5%) 1
    Nervous system disorders
    Headache1/65 (1.5%) 1
    Reproductive system and breast disorders
    Enlarged Prostate1/65 (1.5%) 1
    Vascular disorders
    Flushing1/65 (1.5%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitlePrithviraj Bose MD/Associate Porfessor
    OrganizationThe University of Texas MD Anderson Cancer Center
    Phone713-792-7747
    EmailPBose@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03019939
    Other Study ID Numbers:
    • 2016-0373
    • NCI-2017-00323
    • 2016-0373
    First Posted:
    Jan 13, 2017
    Last Update Posted:
    Oct 26, 2021
    Last Verified:
    Oct 1, 2021