Liposomal Amphotericin B (Ambisome) Versus Oral Voriconazole for the Prevention of Invasive Fungal Infections - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00418951

Purpose

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 AML or MDS who are receiving chemotherapy. The safety of these treatments will also be studied and compared.

Condition	Intervention	Phase
Acute Myelogenous Leukemia Myelodysplastic Syndrome	Drug: Voriconazole Drug: Liposomal amphotericin B	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title:	Open, Randomized Comparative Trial of Two Different Schedules of Liposomal Amphotericin B Versus Oral Voriconazole for the Prevention of Invasive Fungal Infections

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fungal Infections Leukemia, Adult Acute Leukemia, Adult Chronic Molds

Drug Information available for: Voriconazole Amphotericin B

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Infection Rate [ Time Frame: 35 days from the start of therapy for induction patients and 42 days for salvage patients. ] [ Designated as safety issue: No ]
Toxicity Rate [ Time Frame: 35 days from the start of therapy for induction patients and 42 days for salvage patients. ] [ Designated as safety issue: Yes ]

Enrollment:	120
Study Start Date:	November 2006
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Liposomal amphotericin B: 3 mg/kg: Experimental	Drug: Liposomal amphotericin B 3 mg/kg intravenously three times per week over 2 hours +/- 15 minutes
Liposomal amphotericin B: 9 mg/kg: Experimental	Drug: Liposomal amphotericin B 9 mg/kg intravenously once per week over 2 hours +/- 15 minutes
Voriconazole: 400 mg: Experimental	Drug: Voriconazole 400 mg by mouth twice daily on day 1, followed by 200 mg by mouth twice daily

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418951

Locations

United States, Texas
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

More Information

Additional Information:

M.D. Anderson's website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	U.T. M.D. Anderson Cancer Center ( Jorge Cortes, MD / Professor )
Study ID Numbers:	2006-0536
Study First Received:	January 3, 2007
Last Updated:	December 14, 2009
ClinicalTrials.gov Identifier:	NCT00418951 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Voriconazole
Vfend
Liposomal amphotericin B
Ambisome

Acute Myelogenous Leukemia
Myelodysplastic Syndrome
AML
MDS

Additional relevant MeSH terms:

Abelcet
Anti-Infective Agents
Antiprotozoal Agents
Precancerous Conditions
Leukemia, Myeloid, Acute
Infection
Liposomal amphotericin B
Anti-Bacterial Agents
Mycoses
Leukemia
Preleukemia
Antiparasitic Agents
Pathologic Processes
Antifungal Agents

Syndrome
Therapeutic Uses
Voriconazole
Antibiotics, Antifungal
Amebicides
Amphotericin B
Neoplasms by Histologic Type
Disease
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Pharmacologic Actions
Neoplasms
Bone Marrow Diseases

ClinicalTrials.gov processed this record on February 09, 2010