Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: micafungin
Micafungin 100 mg intravenously once daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy.
|
| Experimental: 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). |
Drug: posaconazole
Posaconazole 400 mg orally twice daily. Randomized treatment will be initiated 24-48 h after completion of the last dose of chemotherapy.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- Astellas Pharma US, Inc.
Investigators
- Principal Investigator: Genovefa Papanicolaou, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 10-038
Study Results
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 |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Micafungin | Posaconazole |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 58 | 55 |
| COMPLETED | 51 | 53 |
| NOT COMPLETED | 7 | 2 |
Baseline Characteristics
| Arm/Group Title | Micafungin | Posaconazole | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 58 | 55 | 113 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
61
|
59
|
61
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
25
43.1%
|
26
47.3%
|
51
45.1%
|
| Male |
33
56.9%
|
29
52.7%
|
62
54.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
1.7%
|
5
9.1%
|
6
5.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
6
10.3%
|
3
5.5%
|
9
8%
|
| White |
50
86.2%
|
43
78.2%
|
93
82.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
1.7%
|
4
7.3%
|
5
4.4%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
58
100%
|
55
100%
|
113
100%
|
Outcome Measures
| Title | Time to Failure |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Micafungin | Posaconazole |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 58 | 55 |
| Median (Inter-Quartile Range) [Days] |
16
|
13
|
| Title | To Compare the Number of Days on Study Drug Between Patients Who Receive Posaconazole and Patients Who Receive Micafungin. |
|---|---|
| Description | |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Results reflect patients who discontinued prophylaxis for suspected IFI (invasive fungal infection) |
| Arm/Group Title | Micafungin | Posaconazole |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 58 | 55 |
| Median (Inter-Quartile Range) [days] |
11
|
12
|
| Title | 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 |
|---|---|
| Description | |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Micafungin | Posaconazole |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 58 | 55 |
| Count of Participants [Participants] |
5
8.6%
|
3
5.5%
|
| Title | Prophylaxis Failure of Study Medication for Any Reason Between Patients Who Receive Posaconazole and Those Who Receive Micafungin. |
|---|---|
| Description | |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Micafungin | Posaconazole |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 58 | 55 |
| Prophylaxis failure |
20
34.5%
|
29
52.7%
|
| No prophylaxis failure |
38
65.5%
|
26
47.3%
|
| Title | To Compare Overall Survival Rates at 6 Weeks |
|---|---|
| Description | |
| Time Frame | 6 weeks from randomization between the two treatment arms. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Micafungin | Posaconazole |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 58 | 55 |
| Count of Participants [Participants] |
7
12.1%
|
2
3.6%
|
Adverse Events
| Time Frame | 2 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Micafungin | Posaconazole | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| Micafungin | Posaconazole | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/58 (12.1%) | 2/55 (3.6%) | ||
Serious Adverse Events |
||||
| Micafungin | Posaconazole | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/58 (37.9%) | 11/55 (20%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile Neutropenia | 4/58 (6.9%) | 3/55 (5.5%) | ||
| Blood and lymphatic system disorders - Other, spec | 0/58 (0%) | 1/55 (1.8%) | ||
| Cardiac disorders | ||||
| Cardiac Arrest | 0/58 (0%) | 1/55 (1.8%) | ||
| Restrictive cardiomyopathy | 0/58 (0%) | 1/55 (1.8%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal Disorder | 2/58 (3.4%) | 0/55 (0%) | ||
| Oral Pain | 2/58 (3.4%) | 0/55 (0%) | ||
| Diarrhea | 0/58 (0%) | 1/55 (1.8%) | ||
| General disorders | ||||
| Fever | 2/58 (3.4%) | 2/55 (3.6%) | ||
| Multi-organ failure | 1/58 (1.7%) | 0/55 (0%) | ||
| Death NOS | 0/58 (0%) | 1/55 (1.8%) | ||
| Immune system disorders | ||||
| Immune system disorders - Other, specify | 1/58 (1.7%) | 0/55 (0%) | ||
| Allergic reaction | 0/58 (0%) | 1/55 (1.8%) | ||
| Infections and infestations | ||||
| Infections and infestations - Other, specify | 6/58 (10.3%) | 2/55 (3.6%) | ||
| Sepsis | 3/58 (5.2%) | 0/55 (0%) | ||
| Upper respiratory infection | 3/58 (5.2%) | 1/55 (1.8%) | ||
| Investigations | ||||
| Bilirubin Increased | 1/58 (1.7%) | 0/55 (0%) | ||
| Platelet count decreased | 0/58 (0%) | 4/55 (7.3%) | ||
| Metabolism and nutrition disorders | ||||
| Hypophosphatemia | 0/58 (0%) | 1/55 (1.8%) | ||
| Hypomagnesemia | 0/58 (0%) | 1/55 (1.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 1/58 (1.7%) | 0/55 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 1/58 (1.7%) | 0/55 (0%) | ||
| Sore throat | 1/58 (1.7%) | 0/55 (0%) | ||
| Pneumonitis | 0/58 (0%) | 1/55 (1.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash maculo-papular | 1/58 (1.7%) | 0/55 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Micafungin | Posaconazole | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/58 (0%) | 0/55 (0%) | ||
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 | Dr. Genovefa Papanicolaou MD |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 212-639-8361 |
| papanicg@mskcc.org |
- 10-038