Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT)
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10021 |
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.- 17-112
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Isavuconazole Prophylaxis |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 99 |
| COMPLETED | 95 |
| NOT COMPLETED | 4 |
Baseline Characteristics
| Arm/Group Title | Isavuconazole Prophylaxis |
|---|---|
| Arm/Group Description | 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 Participants | 95 |
| 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
| Title | Clinical Failure of Isavuconazole Prophylaxis by Week + 14 Post Hematopoietic Stem Cell Transplant (HCT) |
|---|---|
| Description | 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. |
| Time Frame | 14 weeks post HCT |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Isavuconazole Prophylaxis |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 95 |
| 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%
|
| Title | Clinical Failure of Isavuconazole Prophylaxis by Week + 26 Post Hematopoietic Stem Cell Transplant (HCT) |
|---|---|
| Description | 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. |
| Time Frame | 26 weeks post HCT |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Isavuconazole Prophylaxis |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 95 |
| Completed Study |
89
93.7%
|
| Did Not Complete Study d/t Death |
6
6.3%
|
Adverse Events
| Time Frame | 14 weeks | |
|---|---|---|
| Adverse Event Reporting Description | AE's leading to Isavuconazole discontinuation were collected | |
| Arm/Group Title | Isavuconazole Prophylaxis | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Isavuconazole Prophylaxis | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/95 (6.3%) | |
Serious Adverse Events |
||
| Isavuconazole Prophylaxis | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/95 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Isavuconazole Prophylaxis | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/95 (7.4%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 1/95 (1.1%) | |
| Gastrointestinal disorders | ||
| Nausea | 1/95 (1.1%) | |
| Hepatobiliary disorders | ||
| Transaminitis | 2/95 (2.1%) | |
| Investigations | ||
| Hyperbilirubinemia | 3/95 (3.2%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1/95 (1.1%) | |
Limitations/Caveats
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/Title | Genovefa Papanicolaou MD |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 212-639-8361 |
| papanicg@mskcc.org |
- 17-112