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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00418951
First received: January 3, 2007
Last updated: August 1, 2012
Last verified: August 2012
  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 acute myeloid leukemia (AML) or myelodysplastic syndromes 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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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:


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

Primary Outcome Measures:
  • Number of Participants With Invasive Fungal Infection [ Time Frame: 35 days from the start of therapy for induction participants and 42 days for salvage participants. ] [ Designated as safety issue: No ]
    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.


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
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 Name: Ambisome
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 Name: Ambisome
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 Name: Vfend

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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00418951     History of Changes
Other Study ID Numbers: 2006-0536
Study First Received: January 3, 2007
Results First Received: April 15, 2011
Last Updated: August 1, 2012
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:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Mycoses
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Amphotericin B
Liposomal amphotericin B
Voriconazole
14-alpha Demethylase Inhibitors
Amebicides
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014