Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
MICAFUNGIN, POSACONAZOLE, antifungal, prolonged neutropenia, 10-038
Brief summary
The purpose of this study is to compare the effects, good and/or bad, of posaconazole and micafungin in preventing fungal infections after chemotherapy for acute leukemia or myelodysplastic syndrome. When people take chemotherapy, they are more likely to get infections. Posaconazole has been approved for the prevention of fungal infections in patients who receive induction chemotherapy for acute leukemia and myelodysplastic syndrome. Posaconazole is available only as an oral suspension and has to be given with food. After chemotherapy, many patients are not able to tolerate food or oral medication because of severe mucositis. Patients unable to tolerate food and oral medications cannot take posaconazole. Micafungin is an antifungal medication that is given only intravenously. Micafungin is approved for the treatment of certain fungal infections and for preventing fungal infections in patients who receive bone marrow transplant. The investigators know that micafungin is safe. Micafungin has not been tested for the prevention of fungal infections in patients receiving chemotherapy for acute leukemia and myelodysplastic syndrome. Because micafungin is given by vein, it can be given even in patients who cannot take food or medications by mouth after chemotherapy. In this study the investigators want to compare micafungin to posaconazole when given for the prevention of fungal infections in leukemia and myelodysplastic syndrome patients.
Interventions
DRUGmicafungin
Micafungin 100 mg intravenously once daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy.
DRUGposaconazole
Posaconazole 400 mg orally twice daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy.
Sponsors
Astellas Pharma US, Inc.
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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. Disease definition: * Anticipated or documented prolonged neutropenia (ANC\<500/mm3 \[0.5x109/L\]) at baseline or likely to develop within 3 to 5 days and lasting for at least 7 days due to: * Intensive induction chemotherapy for new diagnosis of acute myelogenous leukemia, acute lymphocytic leukemia or myelodysplastic syndrome receiving standard anthracycline based chemotherapy * Re-induction of acute myelogenous or lymphocytic leukemia after primary relapse * Myelodysplastic syndromes requiring induction (myelosuppressive) chemotherapy * Female subjects of childbearing potential must have a negative serum pregnancy test as per MSKCC guidelines. * Able to swallow oral medications
Exclusion criteria
* Subjects with history of presumed or proven invasive fungal infection within 30 days of randomization. * Subjects who are taking the following: Drugs known to interact with posaconazole and that may lead to life-threatening side effects (terfenadine, cisapride, and ebastine at entry or within 24 hours before entry, or astemizole at entry or within 10 days before entry); b. Drugs known to lower the serum concentration/efficacy of posaconazole: cimetidine, rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, and isoniazid at entry or within 24 hours before entry; c. Subjects who are planned to receive \> 2mg flat dose of vinca alkaloids. * Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents. * Subjects with renal insufficiency (estimated creatinine clearance less than 20 mL/minute at baseline or likely to require dialysis during the study). * Subjects having an electrocardiogram with a prolonged QTc interval by manual reading: QTc greater than 490 msec. * Subjects with moderate or severe liver dysfunction at baseline, defined as aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase levels greater than 5 times the upper limit of normal (ULN), or a total bilirubin level greater than 3 times the ULN. * Subjects who are undergoing re-induction chemotherapy and have participated in this study during their first induction chemotherapy. * Subjects who will be receiving dasatinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Failure | 2 years | Clinical failure is defined as: 1) need for systemic antifungal therapy (AmBisome) for \> 3 consecutive days for presumptive fungal infection, toxicity or intolerance of study medication or 2) death. |
Secondary
| Measure | Time frame |
|---|---|
| To Compare the Number of Days on Study Drug Between Patients Who Receive Posaconazole and Patients Who Receive Micafungin. | 2 years |
| To Compare the Incidence of Possible, Probable or Proven Invasive Fungal Infections Between Patients Who Receive Posaconazole and Those Who Receive Micafungin During Treatment Phase | 2 years |
| Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin. | 2 years |
| To Compare Overall Survival Rates at 6 Weeks | 6 weeks from randomization between the two treatment arms. |
Countries
United States
Participant flow
Recruitment details
Protocol Open to Accrual 09/09/2010 Protocol Closed to Accrual 04/20/2016 Primary Completion Date 04/20/2016 Recruitment Location is the medical clinic
Participants by arm
| Arm | Count |
|---|---|
| Micafungin This is a single institution (MSKCC), randomized, open-label comparative trial of micafungin and posaconazole administered as prophylaxis against fungal infections during neutropenia following induction chemotherapy for myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS).
micafungin: Micafungin 100 mg intravenously once daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy. | 58 |
| Posaconazole This is a single institution (MSKCC), randomized, open-label comparative trial of micafungin and posaconazole administered as prophylaxis against fungal infections during neutropenia following induction chemotherapy for myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS).
posaconazole: Posaconazole 400 mg orally twice daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy. | 55 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 2 |
Baseline characteristics
| Characteristic | Micafungin | Total | Posaconazole |
|---|---|---|---|
| Age, Continuous | 61 years | 61 years | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 50 Participants | 93 Participants | 43 Participants |
| Region of Enrollment United States | 58 Participants | 113 Participants | 55 Participants |
| Sex: Female, Male Female | 25 Participants | 51 Participants | 26 Participants |
| Sex: Female, Male Male | 33 Participants | 62 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 58 | 2 / 55 |
| other Total, other adverse events | 0 / 58 | 0 / 55 |
| serious Total, serious adverse events | 22 / 58 | 11 / 55 |
Outcome results
Primary
Time to Failure
Clinical failure is defined as: 1) need for systemic antifungal therapy (AmBisome) for \> 3 consecutive days for presumptive fungal infection, toxicity or intolerance of study medication or 2) death.
Time frame: 2 years
Population: Analysis based on a modified intention-to-treat (mITT) approach, with the use of data from patients who underwent randomization and received 2 or more doses of prophylaxis. Trial designed w/ power to detect absolute differences of \~25% of prophylaxis failure in the two groups with \~ 80% power and a significance level of 5% using a two-tail test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Micafungin | Time to Failure | 16 Days |
| Posaconazole | Time to Failure | 13 Days |
Secondary
Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Micafungin | Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin. | Prophylaxis failure | 20 Participants |
| Micafungin | Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin. | No prophylaxis failure | 38 Participants |
| Posaconazole | Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin. | Prophylaxis failure | 29 Participants |
| Posaconazole | Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin. | No prophylaxis failure | 26 Participants |
Secondary
To Compare Overall Survival Rates at 6 Weeks
Time frame: 6 weeks from randomization between the two treatment arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Micafungin | To Compare Overall Survival Rates at 6 Weeks | 7 Participants |
| Posaconazole | To Compare Overall Survival Rates at 6 Weeks | 2 Participants |
Secondary
To Compare the Incidence of Possible, Probable or Proven Invasive Fungal Infections Between Patients Who Receive Posaconazole and Those Who Receive Micafungin During Treatment Phase
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Micafungin | To Compare the Incidence of Possible, Probable or Proven Invasive Fungal Infections Between Patients Who Receive Posaconazole and Those Who Receive Micafungin During Treatment Phase | 5 Participants |
| Posaconazole | To Compare the Incidence of Possible, Probable or Proven Invasive Fungal Infections Between Patients Who Receive Posaconazole and Those Who Receive Micafungin During Treatment Phase | 3 Participants |
Secondary
To Compare the Number of Days on Study Drug Between Patients Who Receive Posaconazole and Patients Who Receive Micafungin.
Time frame: 2 years
Population: Results reflect patients who discontinued prophylaxis for suspected IFI (invasive fungal infection)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Micafungin | To Compare the Number of Days on Study Drug Between Patients Who Receive Posaconazole and Patients Who Receive Micafungin. | 11 days |
| Posaconazole | To Compare the Number of Days on Study Drug Between Patients Who Receive Posaconazole and Patients Who Receive Micafungin. | 12 days |