Oral Posaconazole Three Times Per Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC)

Condition(s) targeted: Invasive Fungal Infections; Hematologic Malignancies

Intervention: Posaconazole (Drug); Amphotericin B Liquid Complex (ABLC) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Issam Raad, MD/Professor, Principal Investigator, Affiliation: U.T. M.D. Anderson Cancer Center

Overall contact:
Issam Raad, MD/Professor, Phone: 713-792-7943

The objective of this study is to compare the safety and efficacy of ABLC versus oral Posaconazole in the prevention of invasive fungal infections in high risk patients with hematologic malignancies or hematopoietic stem cell transplant.

Official title: Phase III Clinical Trial of Oral Posaconazole 3 Times/Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC) for Prevention of Invasive Fungal Infections In Patients With Hematologic Malignancies & Hematopoietic Stem Cell Transplant

Study design: Treatment, Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: To compare Noxafil (posaconazole) to Amphotericin B Liquid Complex (ABLC) in patients having blood cancer and/or had a recent/upcoming bone marrow transplant to learn if posaconazole will provide same or better results as ABLC preventing IFIs.

Secondary outcome: The safety of these drugs will also be studied.

Detailed description: The Study Drugs:

ABLC is an antifungal drug that is commonly used to treat and/or prevent a variety of serious invasive fungal infections (IFIs). In this study, ABLC will be used for IFI prevention.

Posaconazole is a newer antifungal drug that is commonly used to prevent serious IFIs.

Screening Tests:

Before you can receive the study treatment, you will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests will be performed:

- If the study doctor and/or your primary doctor feel it is necessary, you will be checked

for signs of IFI (such as fever and pain).

- You will be asked about your medical and surgical history.

- You will be asked about any medications you may have taken in the past 4 weeks.

- You will have a physical exam, including measurement of your vital signs (heart rate,

temperature, breathing rate, blood pressure), weight, and height.

- You will have an electrocardiogram (ECG -- a test that measures the electrical activity

of the heart).

- Blood (about 1 tablespoon) will be drawn for routine tests. Throughout the study, these

routine blood sample may be drawn from your central venous catheter (CVC), if you have one in place at the time.

- Women who are able to have children must have a negative blood (about 1 teaspoon) or

negative urine pregnancy test.

If your study doctor and/or primary doctor feel it is necessary to make sure you do not already have an IFI, you will have certain routine diagnostic tests performed. These tests may include a blood draw (about 1 tablespoon), scans (such as x-rays or computed tomography [CT] scans), skin tissue biopsy, and/or a bronchoscopy. You will sign a separate consent for these standard procedures.

To perform a skin tissue biopsy, an area of the skin is numbed with anesthetic, and a small amount of skin is removed with a special knife.

To perform a bronchoscopy, you will be given drugs to relax, and then a local anesthetic will be sprayed into your nose and throat to numb those areas. A thin, flexible tube with a light will be placed through your nose or mouth and into your lungs. A small brush will be fed through the tube and into your lungs. The brush will gently scrape off samples of lung tissue. Tweezers will then be fed through the tube to collect the tissue samples. A small amount of water will be sprayed into your lungs and then suctioned out through the tube to collect additional tissue samples, mucous samples, and fluid samples if necessary.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to receive either posaconazole or ABLC. You will have an equal chance (50/50) of being assigned to either group. You and your study doctor will know which group you are in.

Study Drug Administration:

If you are assigned to the Posaconazole Group, you will take posaconazole 3 times a day by mouth for up to 6 weeks (Days 1-42). The study doctor will advise you about taking it with fatty meals and/or nutritional supplements.

If you are assigned to the ABLC Group, you will receive ABLC once a week by vein over 4-6 hours, for up to 6 weeks (from Day 1 through Day 42). The drug may be given in the hospital (if you are admitted to the hospital before or during the study) or at an outpatient treatment center.

Study Visits:

Once a week from Day 1 to Day 42, you will have the following procedures performed:

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any medications and treatments you may be receiving.

- You will be asked about any IFI symptoms that may have developed. You will also be

asked about any side effects that may have occurred since your last visit. (You should contact the study doctor and/or study staff right away, if at any time you feel you have had a side effect.)

If your doctor feels it is necessary at any time in the study, you will have an ECG.

You may have certain routine diagnostic tests performed at any time in the study, if necessary to confirm you do not have an IFI. These tests may include blood collection (about 1 tablespoon), scans, skin tissue biopsy, and/or bronchoscopy.

Length of Study:

You will receive study treatment for up to 6 weeks (42 days). If you develop an IFI or any intolerable side effects, you will be taken off study early. You may also be taken off study if your neutrophil (a type of white blood cell) counts recover.

End-of-Treatment Visit:

Within 7-14 days after the last dose of study medication, you will have an end-of-treatment visit with the following procedures performed.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have a physical exam, including measurement of vital signs.

- If the study doctor and/or your primary doctor thinks you may have an IFI, routine

diagnostic tests may be performed.

Follow-up Visit:

Four weeks after your last dose of study medication, you will have a follow-up visit with the following procedures performed:

- You will be checked for any signs of IFI.

- If your doctor suspects you have an IFI, a scan (such as an x-ray or CT scan) and/or

bronchoscopy may be performed.

- You will be asked about any medications and treatments you may be receiving, and any

side effects you may have had.

- Your vital signs will be checked, and a physical exam may be performed.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- An ECG may be performed.

This is an investigational study. ABLC and posaconazole are FDA approved and commercially available for the treatment and prevention of IFIs. Posaconazole is FDA approved for the way it is being used in this study. The study dose and study schedule for ABLC, however, is considered experimental. Currently, this dose and schedule for ABLC is being used in research only.

Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Subjects: 18 years of age or above.

2. Disease definition: Anticipated or documented prolonged neutropenic (ANC<500) at Baseline or likely to develop within 3 to 5 days and lasting for at least 7 days due to: 1) Hematopoietic stem cell transplant; 2) Intensive induction-remission chemotherapy for a new diagnosis of acute leukemia, myelodysplastic syndrome; 3) Reinduction of acute leukemia after primary relapse 4) Lymphoma requiring induction chemotherapy.

3. Subjects must be willing to give written informed consent and able to adhere to dosing and study visit schedule.

4. Female subjects of childbearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) at Baseline or within 96 hours before the start of study drug.

5. Female subjects of childbearing potential must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 30 days after stopping the medication. Acceptable methods of contraception include condoms with/without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD (intrauterine device), oral/injectable hormonal contraceptive, surgical sterilization (e. g. hysterectomy/tubal ligation).

Exclusion Criteria:

1. Subjects previously treated with antifungal therapy (voriconazole, fluconazole, or itraconazole) for proven or probable IFI within 30 days of enrollment.

2. Subjects who have taken the following drugs that are known to interact with azoles and that may lead to life-threatening side effects: terfenadine, cisapride, primozide, and ebastine at entry or within 24 hours before entry, or astemizole at entry or within 7 days before entry).

3. Subjects who have taken the following drugs that are known to lower the serum concentration/efficacy of azole antifungal agents: cimetidine, rifampin, carbamezapine, phenytoin, rifabutin, barbiturates, isoniazid, and vinca alkaloids (vincristine, vinblastine) at entry or within 24 hours before entry.

4. Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents or Amphotericin B.

5. Patients who are unable to take pills.

6. Subjects with proven or probable invasive fungal infection.

7. Subjects with renal insufficiency (estimated creatine clearance less than 20mL/minute at Baseline or likely to require dialysis during the study).

8. Subjects having ECG with a prolonged QTc interval by manual reading: QTc greater than 500 msec. at Baseline.

9. Subjects with moderate or severe liver dysfunction at baseline, defined as aspartate amniotransferase (AST), alanine amniotransferase (ALT) and / or a total bilirubin level greater than 3 times the upper limit of normal (ULN).

10. Women who are breast feeding, pregnant, or intend to become pregnant during the course of the study.

11. Prior enrollment in this study.

Issam Raad, MD/Professor, Phone: 713-792-7943

U.T. M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting

U.T. M.D. Anderson website

Starting date: August 2008
Last updated: September 10, 2008