Hematologic Malignancy, Myeloproliferative Disorder
Conditions
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).
Interventions
DRUGIsavuconazole
Intravenous or oral: Isavuconazonium sulfate 372 mg Q 8hour for 6 doses as loading dose, followed by 372 mg Q day as maintenance dose.
Sponsors
Astellas Pharma US, Inc.
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) | 14 weeks post HCT | Clinical failure is measured by: 1. Systemic antifungal therapy for \> 14 consecutive days for suspected fungal infection up to week 14. 2. Breakthrough proven or probable fungal infection during the prophylaxis phase.\* 3. Toxicity leading to permanent discontinuation of prophylaxis 4. 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. |
| Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT) | 26 weeks post HCT | Clinical failure is measured by: 1. Systemic antifungal therapy for \> 14 consecutive days for suspected fungal infection up to week 14. 2. Breakthrough proven or probable fungal infection during the prophylaxis phase.\* 3. Toxicity leading to permanent discontinuation of prophylaxis 4. 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 95 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated | 4 |
Baseline characteristics
| Characteristic | Isavuconazole Prophylaxis |
|---|---|
| Age, Continuous | 57 years |
| Conditioning Regimen Intensity Myeloablative | 53 Participants |
| Conditioning Regimen Intensity Non-myeloablative | 13 Participants |
| Conditioning Regimen Intensity Reduced intensity | 29 Participants |
| Donor Type Haploidentical | 14 Participants |
| Donor Type Matched related | 19 Participants |
| Donor Type Matched unrelated | 36 Participants |
| Donor Type Mismatched related/unrelated | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Graft Manipulation Ex vivo T-cell depletion (CD4+ selected) | 31 Participants |
| Graft Manipulation No graft manipulation | 64 Participants |
| Graft versus Host Disease (GvHD) Prophylaxis Cyclophosphamide+Mycophenolate+Tacrolimus or Si*** | 22 Participants |
| Graft versus Host Disease (GvHD) Prophylaxis Cyclosporine + Mycophenolate Mofetil** | 16 Participants |
| Graft versus Host Disease (GvHD) Prophylaxis Ex vivo T-cell depletion | 29 Participants |
| Graft versus Host Disease (GvHD) Prophylaxis Tacrolimus + Methotrexate* | 26 Participants |
| Graft versus Host Disease (GvHD) Prophylaxis Tacrolimus + Mycophenolate Mofetil | 2 Participants |
| Hematopoietic cell transplant (HCT) Source Bone marrow | 17 Participants |
| Hematopoietic cell transplant (HCT) Source Cord blood | 14 Participants |
| Hematopoietic cell transplant (HCT) Source Peripheral blood (PBSC) | 64 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 81 Participants |
| Region of Enrollment United States | 95 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 64 Participants |
| Underlying Disease Leukemia | 51 Participants |
| Underlying Disease Lymphoma | 16 Participants |
| Underlying Disease Myelodysplastic syndrome | 15 Participants |
| Underlying Disease Other hematologic malignancy | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 95 |
| other Total, other adverse events | 7 / 95 |
| serious Total, serious adverse events | 0 / 95 |
Outcome results
Primary
Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT)
Clinical failure is measured by: 1. Systemic antifungal therapy for \> 14 consecutive days for suspected fungal infection up to week 14. 2. Breakthrough proven or probable fungal infection during the prophylaxis phase.\* 3. Toxicity leading to permanent discontinuation of prophylaxis 4. 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 frame: 14 weeks post HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Isavuconazole Prophylaxis | Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) | Completed Treatment | 81 Participants |
| Isavuconazole Prophylaxis | Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) | Did not complete treatment, breakthrough IFI | 3 Participants |
| Isavuconazole Prophylaxis | Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) | Did not complete treatment, discont d/t toxicity | 7 Participants |
| Isavuconazole Prophylaxis | Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) | Did not complete treatment, other reasons | 4 Participants |
Primary
Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT)
Clinical failure is measured by: 1. Systemic antifungal therapy for \> 14 consecutive days for suspected fungal infection up to week 14. 2. Breakthrough proven or probable fungal infection during the prophylaxis phase.\* 3. Toxicity leading to permanent discontinuation of prophylaxis 4. 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 frame: 26 weeks post HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Isavuconazole Prophylaxis | Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT) | Completed Study | 89 Participants |
| Isavuconazole Prophylaxis | Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT) | Did Not Complete Study d/t Death | 6 Participants |