Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT)

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT03149055
Collaborator
Astellas Pharma US, Inc. (Industry)
99
Enrollment
1
Location
1
Arm
54.2
Actual Duration (Months)
1.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to study the effects of isavuconazole in preventing fungal infections in patients who have had a hematopoietic stem cell transplant (HCT).

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
99 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single Center, Open-label Trial of Isavuconazole Prophylaxis Against Invasive Fungal Infection in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT)
Actual Study Start Date :
May 4, 2017
Actual Primary Completion Date :
Aug 20, 2019
Actual Study Completion Date :
Nov 8, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Isavuconazole prophylaxis

Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose. The minimum duration of prophylaxis with isavuconazole will be through D +60. Beyond day +60 discontinuation is at the discretion of the treating physician.

Drug: Isavuconazole
Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
Other Names:
  • Isavuconazonium sulfate
  • Outcome Measures

    Primary Outcome Measures

    1. Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) [14 weeks post HCT]

      Clinical failure is measured by: Systemic antifungal therapy for > 14 consecutive days for suspected fungal infection up to week 14. Breakthrough proven or probable fungal infection during the prophylaxis phase.* Toxicity leading to permanent discontinuation of prophylaxis Adverse event requiring discontinuation. The prophylaxis phase was defined as the period from the first dose of isavuconazole through 7 days after discontinuation of isavuconazole.

    2. Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT) [26 weeks post HCT]

      Clinical failure is measured by: Systemic antifungal therapy for > 14 consecutive days for suspected fungal infection up to week 14. Breakthrough proven or probable fungal infection during the prophylaxis phase.* Toxicity leading to permanent discontinuation of prophylaxis Adverse event requiring discontinuation. The prophylaxis phase was defined as the period from the first dose of isavuconazole through 7 days after discontinuation of isavuconazole.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subjects of greater than or equal to 18 years of age of either sex and of any race.

    • Have received first peripheral blood, marrow or cord blood transplant from a family or unrelated donor for hematologic malignancy or myeloproliferative disorder.

    Exclusion Criteria:
    • Proven or probable aspergillosis or other mold infection or deep mycoses including hepatosplenic candidiasis less than 60 days from first dose of ISA.

    • History of allergy or intolerance to ISA.

    • Clinically significant elevation of liver function tests prior to the first day of dosing (FDD) that at the discretion of the treating physician would preclude the administration of an azole antifungal.

    • Familial short QT syndrome.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10021

    Sponsors and Collaborators

    • Memorial Sloan Kettering Cancer Center
    • Astellas Pharma US, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Memorial Sloan Kettering Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03149055
    Other Study ID Numbers:
    • 17-112
    First Posted:
    May 11, 2017
    Last Update Posted:
    Nov 17, 2021
    Last Verified:
    Nov 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 Details
    Pre-assignment Detail
    Arm/Group TitleIsavuconazole Prophylaxis
    Arm/Group DescriptionIntravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose. The minimum duration of prophylaxis with isavuconazole will be through D +60. Beyond day +60 discontinuation is at the discretion of the treating physician. Isavuconazole: Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
    Period Title: Overall Study
    STARTED99
    COMPLETED95
    NOT COMPLETED4

    Baseline Characteristics

    Arm/Group TitleIsavuconazole Prophylaxis
    Arm/Group DescriptionIntravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose. The minimum duration of prophylaxis with isavuconazole will be through D +60. Beyond day +60 discontinuation is at the discretion of the treating physician. Isavuconazole: Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
    Overall Participants95
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    57
    Sex: Female, Male (Count of Participants)
    Female
    31
    32.6%
    Male
    64
    67.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    9
    9.5%
    Not Hispanic or Latino
    77
    81.1%
    Unknown or Not Reported
    9
    9.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    6
    6.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    7
    7.4%
    White
    81
    85.3%
    More than one race
    0
    0%
    Unknown or Not Reported
    1
    1.1%
    Region of Enrollment (Count of Participants)
    United States
    95
    100%
    Underlying Disease (Count of Participants)
    Leukemia
    51
    53.7%
    Myelodysplastic syndrome
    15
    15.8%
    Lymphoma
    16
    16.8%
    Other hematologic malignancy
    13
    13.7%
    Graft Manipulation (Count of Participants)
    Ex vivo T-cell depletion (CD4+ selected)
    31
    32.6%
    No graft manipulation
    64
    67.4%
    Donor Type (Count of Participants)
    Matched related
    19
    20%
    Matched unrelated
    36
    37.9%
    Mismatched related/unrelated
    26
    27.4%
    Haploidentical
    14
    14.7%
    Hematopoietic cell transplant (HCT) Source (Count of Participants)
    Peripheral blood (PBSC)
    64
    67.4%
    Bone marrow
    17
    17.9%
    Cord blood
    14
    14.7%
    Conditioning Regimen Intensity (Count of Participants)
    Myeloablative
    53
    55.8%
    Non-myeloablative
    13
    13.7%
    Reduced intensity
    29
    30.5%
    Graft versus Host Disease (GvHD) Prophylaxis (Count of Participants)
    Tacrolimus + Methotrexate*
    26
    27.4%
    Cyclosporine + Mycophenolate Mofetil**
    16
    16.8%
    Tacrolimus + Mycophenolate Mofetil
    2
    2.1%
    Cyclophosphamide+Mycophenolate+Tacrolimus or Si***
    22
    23.2%
    Ex vivo T-cell depletion
    29
    30.5%

    Outcome Measures

    1. Primary Outcome
    TitleClinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT)
    DescriptionClinical failure is measured by: Systemic antifungal therapy for > 14 consecutive days for suspected fungal infection up to week 14. Breakthrough proven or probable fungal infection during the prophylaxis phase.* Toxicity leading to permanent discontinuation of prophylaxis Adverse event requiring discontinuation. The prophylaxis phase was defined as the period from the first dose of isavuconazole through 7 days after discontinuation of isavuconazole.
    Time Frame14 weeks post HCT

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleIsavuconazole Prophylaxis
    Arm/Group DescriptionIntravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose. The minimum duration of prophylaxis with isavuconazole will be through D +60. Beyond day +60 discontinuation is at the discretion of the treating physician. Isavuconazole: Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
    Measure Participants95
    Completed Treatment
    81
    85.3%
    Did not complete treatment, breakthrough IFI
    3
    3.2%
    Did not complete treatment, discont d/t toxicity
    7
    7.4%
    Did not complete treatment, other reasons
    4
    4.2%
    2. Primary Outcome
    TitleClinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT)
    DescriptionClinical failure is measured by: Systemic antifungal therapy for > 14 consecutive days for suspected fungal infection up to week 14. Breakthrough proven or probable fungal infection during the prophylaxis phase.* Toxicity leading to permanent discontinuation of prophylaxis Adverse event requiring discontinuation. The prophylaxis phase was defined as the period from the first dose of isavuconazole through 7 days after discontinuation of isavuconazole.
    Time Frame26 weeks post HCT

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleIsavuconazole Prophylaxis
    Arm/Group DescriptionIntravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose. The minimum duration of prophylaxis with isavuconazole will be through D +60. Beyond day +60 discontinuation is at the discretion of the treating physician. Isavuconazole: Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
    Measure Participants95
    Completed Study
    89
    93.7%
    Did Not Complete Study d/t Death
    6
    6.3%

    Adverse Events

    Time Frame14 weeks
    Adverse Event Reporting Description AE's leading to Isavuconazole discontinuation were collected
    Arm/Group TitleIsavuconazole Prophylaxis
    Arm/Group DescriptionIntravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose. The minimum duration of prophylaxis with isavuconazole will be through D +60. Beyond day +60 discontinuation is at the discretion of the treating physician. Isavuconazole: Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
    All Cause Mortality
    Isavuconazole Prophylaxis
    Affected / at Risk (%)# Events
    Total6/95 (6.3%)
    Serious Adverse Events
    Isavuconazole Prophylaxis
    Affected / at Risk (%)# Events
    Total0/95 (0%)
    Other (Not Including Serious) Adverse Events
    Isavuconazole Prophylaxis
    Affected / at Risk (%)# Events
    Total7/95 (7.4%)
    Blood and lymphatic system disorders
    Anemia1/95 (1.1%)
    Gastrointestinal disorders
    Nausea1/95 (1.1%)
    Hepatobiliary disorders
    Transaminitis2/95 (2.1%)
    Investigations
    Hyperbilirubinemia3/95 (3.2%)
    Skin and subcutaneous tissue disorders
    Rash1/95 (1.1%)

    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/TitleGenovefa Papanicolaou MD
    OrganizationMemorial Sloan Kettering Cancer Center
    Phone212-639-8361
    Emailpapanicg@mskcc.org
    Responsible Party:
    Memorial Sloan Kettering Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03149055
    Other Study ID Numbers:
    • 17-112
    First Posted:
    May 11, 2017
    Last Update Posted:
    Nov 17, 2021
    Last Verified:
    Nov 1, 2021