Liposomal Amphotericin B (Ambisome) Versus Oral Voriconazole for the Prevention of Invasive Fungal Infections
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to compare the effectiveness of liposomal amphotericin B given three times per week , versus liposomal amphotericin B given once per week, versus oral voriconazole in the prevention of fungal infections in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes MDS who are receiving chemotherapy. The safety of these treatments will also be studied and compared.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Ambisome and voriconazole are drugs that have been used to fight fungal infections, which typically occur during chemotherapy as a result of lowered immune system functioning. Ambisome works by binding to the sterol component of the fungal cell membrane. This causes "holes" to appear in the membrane, which leads to death of the fungal cell. Voriconazole inhibits an essential step of the biosynthesis of an important component of the fungal cell wall (ergosterol). This causes the impairment of the fungal cell wall.
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will be asked questions about your medical history. You will have a complete physical exam and a chest x-ray. You will have computed tomography (CT) scans of the chest. You will also have about 1 teaspoon of blood drawn for routine tests. Test results from the pregnancy test that you will have before your leukemia treatment will be looked at for this study. You will not have a pregnancy test performed for this study.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to one of 3 treatment groups (Group 1, Group 2, or Group 3). Participants in Groups 1 and 2 will receive treatment with ambisome. Participants in Group 3 will receive treatment with voriconazole. Participants in all 3 groups will begin treatment 24 hours after the last dose of chemotherapy.
If you are assigned to Group 1, you will receive ambisome by vein as a continuous infusion over 2 hours 1 time per day, 3 times each week.
If you are assigned to Group 2, you will receive ambisome by vein as a continuous infusion over 2 hours 1 time per week.
If you are assigned to Group 3, you will take 2 pills by mouth (1 hour after breakfast) and 2 pills by mouth (1 hour after dinner) for 1 day, which amounts to 4 pills in total on Day 1. You will then take 1 pill by mouth (1 hour after breakfast) and 1 pill by mouth (1 hour after dinner) everyday for the remainder of this study, which amounts to 2 pills in total each day.
You will have about 1 teaspoon of blood drawn for routine tests 2 times each week. You will also receive treatment with standard of care medications. These medications (which will be specified by your doctor) will be used to help decrease the risk of developing bacterial infections and viral infections.
If you develop a fever during treatment on this study, you will have a chest x-ray and a CT scan of the chest within 3 days after the fever started.
You may remain on this study for up to 35 days (if you are receiving chemotherapy for the first time) and up to 42 days (if you have had prior chemotherapy). Your participation may end on this study if your study doctor thinks it is necessary, if other antifungal therapy is required, or if you develop any intolerable side effects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Liposomal amphotericin B: 3 mg/kg 3 mg/kg intravenously (IV) three times per week |
Drug: Liposomal amphotericin B
3 mg/kg intravenously three times per week over 2 hours +/- 15 minutes
Other Names:
|
| Experimental: Liposomal amphotericin B: 9 mg/kg 9 mg/kg IV once per week |
Drug: Liposomal amphotericin B
9 mg/kg intravenously once per week over 2 hours +/- 15 minutes
Other Names:
|
| Experimental: Voriconazole: 400 mg 400 mg oral twice daily day 1 followed by 200 mg twice daily |
Drug: Voriconazole
400 mg by mouth twice daily on day 1, followed by 200 mg by mouth twice daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Invasive Fungal Infection [35 days from the start of therapy for induction participants and 42 days for salvage participants.]
Endpoint was whether participant had an invasive fungal infection or not, a potentially fatal complication with leukemia patients. Efficacy defined as absence of proven and probable fungal infection. Probable fungal infection is: 1) Positive radiographic findings consistent with fungal infections documented on CT imaging: Lower respiratory tract infection: halo sign, air crescent-sign, or cavity within areas of consolidation; Sinus: erosion of sinus walls or extension of infection to neighboring structures, extensive skull base destruction; and/or 2) Two positive galactomannan index test.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of AML or high risk MDS undergoing induction chemotherapy or first salvage chemotherapy.
-
Age >/=18 years.
-
Patients must sign an informed consent.
Exclusion Criteria:
-
Patients with history of anaphylaxis attributed to azole or amphotericin B compounds.
-
Patients with clinical or other evidence that indicates that they have proven or probable invasive fungal infection prior to enrollment.
-
Patients with total bilirubin levels > 3 times the upper normal limits (i.e. > 3.0 mg/dl); or serum glutamic pyruvic transaminase (SGPT)> 5 times upper limit normal.
-
Patients with serum creatinine > 2.0 mg/dl.
-
Patients receiving any medication that is contraindicated with the use of voriconazole.
-
Patients who have participated in this study during induction chemotherapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The University of Texas M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
Investigators
- Principal Investigator: Gloria N Mattiuzzi, MD, M.D. Anderson Cancer Center
- Study Director: Gloria N Mattiuzzi, MD, The University of Texas MD Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2006-0536
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: 11/3/2006 to 8/4/09. All patients registered at The University of Texas M.D. Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | Eight of 120 patients registered never received study drug, therefore were excluded from the study. |
| Arm/Group Title | Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg |
|---|---|---|---|
| Arm/Group Description | 3 mg/kg intravenously (IV) three times per week | 9 mg/kg IV once per week | 400 mg oral twice daily day 1 followed by 200 mg twice daily |
| Period Title: Overall Study | |||
| STARTED | 39 | 33 | 40 |
| COMPLETED | 39 | 33 | 40 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg intravenously (IV) three times per week | 9 mg/kg IV once per week | 400 mg oral twice daily day 1 followed by 200 mg twice daily | Total of all reporting groups |
| Overall Participants | 39 | 33 | 40 | 112 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
60
|
71
|
71
|
60
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
19
48.7%
|
16
48.5%
|
19
47.5%
|
54
48.2%
|
| Male |
20
51.3%
|
17
51.5%
|
21
52.5%
|
58
51.8%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
39
100%
|
33
100%
|
40
100%
|
112
100%
|
Outcome Measures
| Title | Number of Participants With Invasive Fungal Infection |
|---|---|
| Description | Endpoint was whether participant had an invasive fungal infection or not, a potentially fatal complication with leukemia patients. Efficacy defined as absence of proven and probable fungal infection. Probable fungal infection is: 1) Positive radiographic findings consistent with fungal infections documented on CT imaging: Lower respiratory tract infection: halo sign, air crescent-sign, or cavity within areas of consolidation; Sinus: erosion of sinus walls or extension of infection to neighboring structures, extensive skull base destruction; and/or 2) Two positive galactomannan index test. |
| Time Frame | 35 days from the start of therapy for induction participants and 42 days for salvage participants. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Outcome evaluability required at least two doses of study drug. |
| Arm/Group Title | Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg |
|---|---|---|---|
| Arm/Group Description | 3 mg/kg intravenously (IV) three times per week | 9 mg/kg IV once per week | 400 mg oral twice daily day 1 followed by 200 mg twice daily |
| Measure Participants | 35 | 28 | 39 |
| Number [participants] |
3
7.7%
|
4
12.1%
|
2
5%
|
Adverse Events
| Time Frame | Three years, ten months. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg | |||
| Arm/Group Description | 3 mg/kg intravenously (IV) three times per week | 9 mg/kg IV once per week | 400 mg oral twice daily day 1 followed by 200 mg twice daily | |||
All Cause Mortality |
||||||
| Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/39 (12.8%) | 2/33 (6.1%) | 4/40 (10%) | |||
| Cardiac disorders | ||||||
| Supravnetricular Tachycardia | 2/39 (5.1%) | 2 | 0/33 (0%) | 0 | 0/40 (0%) | 0 |
| General disorders | ||||||
| Death | 2/39 (5.1%) | 2 | 0/33 (0%) | 0 | 2/40 (5%) | 2 |
| Allergic Reaction | 0/39 (0%) | 0 | 1/33 (3%) | 1 | 0/40 (0%) | 0 |
| Chest Pain | 0/39 (0%) | 0 | 1/33 (3%) | 1 | 0/40 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Hyperbilirubinemia | 1/39 (2.6%) | 1 | 0/33 (0%) | 0 | 1/40 (2.5%) | 1 |
| Elevated alanine aminotransferase | 0/39 (0%) | 0 | 0/33 (0%) | 0 | 1/40 (2.5%) | 1 |
| Infections and infestations | ||||||
| Infection Sepsis | 1/39 (2.6%) | 1 | 0/33 (0%) | 0 | 0/40 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute Renal Failure | 1/39 (2.6%) | 1 | 0/33 (0%) | 0 | 0/40 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute Respiratory Failure | 1/39 (2.6%) | 1 | 0/33 (0%) | 0 | 0/40 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Liposomal Amphotericin B: 3 mg/kg | Liposomal Amphotericin B: 9 mg/kg | Voriconazole: 400 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/39 (0%) | 0/33 (0%) | 0/40 (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 | Jorge Cortes, MD / Professor |
|---|---|
| Organization | The University of Texas MD Anderson Cancer Center |
| Phone | 713-745-5783 |
| eharrison@mdanderson.org |
- 2006-0536