Trial Outcomes & Findings for Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT) (NCT NCT03149055)
NCT ID: NCT03149055
Last Updated: 2025-05-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
99 participants
Primary outcome timeframe
14 weeks post HCT
Results posted on
2025-05-16
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
99
|
|
Overall Study
COMPLETED
|
95
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Not treated
|
4
|
Baseline Characteristics
Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT)
Baseline characteristics by cohort
| Measure |
Isavuconazole Prophylaxis
n=95 Participants
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.
|
|---|---|
|
Age, Continuous
|
57 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
77 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
81 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
95 Participants
n=5 Participants
|
|
Underlying Disease
Leukemia
|
51 Participants
n=5 Participants
|
|
Underlying Disease
Myelodysplastic syndrome
|
15 Participants
n=5 Participants
|
|
Underlying Disease
Lymphoma
|
16 Participants
n=5 Participants
|
|
Underlying Disease
Other hematologic malignancy
|
13 Participants
n=5 Participants
|
|
Graft Manipulation
Ex vivo T-cell depletion (CD4+ selected)
|
31 Participants
n=5 Participants
|
|
Graft Manipulation
No graft manipulation
|
64 Participants
n=5 Participants
|
|
Donor Type
Matched related
|
19 Participants
n=5 Participants
|
|
Donor Type
Matched unrelated
|
36 Participants
n=5 Participants
|
|
Donor Type
Mismatched related/unrelated
|
26 Participants
n=5 Participants
|
|
Donor Type
Haploidentical
|
14 Participants
n=5 Participants
|
|
Hematopoietic cell transplant (HCT) Source
Peripheral blood (PBSC)
|
64 Participants
n=5 Participants
|
|
Hematopoietic cell transplant (HCT) Source
Bone marrow
|
17 Participants
n=5 Participants
|
|
Hematopoietic cell transplant (HCT) Source
Cord blood
|
14 Participants
n=5 Participants
|
|
Conditioning Regimen Intensity
Myeloablative
|
53 Participants
n=5 Participants
|
|
Conditioning Regimen Intensity
Non-myeloablative
|
13 Participants
n=5 Participants
|
|
Conditioning Regimen Intensity
Reduced intensity
|
29 Participants
n=5 Participants
|
|
Graft versus Host Disease (GvHD) Prophylaxis
Tacrolimus + Methotrexate*
|
26 Participants
n=5 Participants
|
|
Graft versus Host Disease (GvHD) Prophylaxis
Cyclosporine + Mycophenolate Mofetil**
|
16 Participants
n=5 Participants
|
|
Graft versus Host Disease (GvHD) Prophylaxis
Tacrolimus + Mycophenolate Mofetil
|
2 Participants
n=5 Participants
|
|
Graft versus Host Disease (GvHD) Prophylaxis
Cyclophosphamide+Mycophenolate+Tacrolimus or Si***
|
22 Participants
n=5 Participants
|
|
Graft versus Host Disease (GvHD) Prophylaxis
Ex vivo T-cell depletion
|
29 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 14 weeks post HCTClinical 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.
Outcome measures
| Measure |
Isavuconazole Prophylaxis
n=95 Participants
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.
|
|---|---|
|
Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT)
Completed Treatment
|
81 Participants
|
|
Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT)
Did not complete treatment, breakthrough IFI
|
3 Participants
|
|
Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT)
Did not complete treatment, discont d/t toxicity
|
7 Participants
|
|
Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT)
Did not complete treatment, other reasons
|
4 Participants
|
PRIMARY outcome
Timeframe: 26 weeks post HCTClinical 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.
Outcome measures
| Measure |
Isavuconazole Prophylaxis
n=95 Participants
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.
|
|---|---|
|
Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT)
Completed Study
|
89 Participants
|
|
Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT)
Did Not Complete Study d/t Death
|
6 Participants
|
Adverse Events
Isavuconazole Prophylaxis
Serious events: 0 serious events
Other events: 7 other events
Deaths: 6 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Isavuconazole Prophylaxis
n=95 participants at risk
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.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
1.1%
1/95 • 14 weeks
AE's leading to Isavuconazole discontinuation were collected
|
|
Gastrointestinal disorders
Nausea
|
1.1%
1/95 • 14 weeks
AE's leading to Isavuconazole discontinuation were collected
|
|
Blood and lymphatic system disorders
Anemia
|
1.1%
1/95 • 14 weeks
AE's leading to Isavuconazole discontinuation were collected
|
|
Hepatobiliary disorders
Transaminitis
|
2.1%
2/95 • 14 weeks
AE's leading to Isavuconazole discontinuation were collected
|
|
Investigations
Hyperbilirubinemia
|
3.2%
3/95 • 14 weeks
AE's leading to Isavuconazole discontinuation were collected
|
Additional Information
Genovefa Papanicolaou MD
Memorial Sloan Kettering Cancer Center
Phone: 212-639-8361
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place