Pharmacokinetics of Posaconazole Prophylaxis in Acute Leukemia

Condition(s) targeted: Leukemia; Fungal Infection

Intervention: Posaconazole (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Jorge Cortes, MD, Study Chair, Affiliation: UT MD Anderson Cancer Center

Overall contact:
Jorge Cortes, MD, Phone: 713-745-2723

The goal of this clinical research study is to learn the amount of posaconazole that is in the body at different time points when given to patients with leukemia. The safety of this drug will also be studied.

Primary Objectives:

To study the plasma pharmacokinetics of posaconazole in relapsed or refractory patients with AML or HR-MDS who will receive salvage chemotherapy.

Secondary Objectives:

To evaluate the safety of posaconazole given as prophylaxis in relapsed or refractory patients with acute leukemia who will receive salvage chemotherapy.

Official title: Phase II Study of the Pharmacokinetics of Posaconazole Prophylaxis in Relapsed or Refractory Patients With Acute Leukemia

Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics Study

Primary outcome: Maximum Observed Concentration in Plasma (Cmax)

Detailed description: Chemotherapy can lower immune system function, which can cause fungal infections to occur more easily. The standard treatment for prevention of such infections includes drugs such as voriconazole and liposomal amphotericin B that help prevent fungus from growing.

The Study Drug:

Posaconazole is designed to block the ergosterol synthesis (a part of the fungal membrane). This may help to prevent fungal infections.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

- Your medical history will be recorded.

- You will have a complete physical exam.

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

- If your doctor thinks it is needed, you will have a chest x-ray or computed tomography

(CT) scan of the chest to check for pneumonia.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take posaconazole by mouth 3 times per day. Posaconazole is a liquid. You should take the study drug after a full meal or with a liquid nutritional supplement (such as a protein shake). If you are not able to eat food, you should take it with a carbonated beverage (such as soda).

Food and Drug Diary:

You will be also be given a food and drug diary where you will write down the time you took each dose. You should also record the time eaten and describe what you ate or drank at each meal. This information will be used to find out the number of calories and amount of protein, carbohydrates, and fat you have consumed. You will be given a small bag where you can keep the drug and diary. You should return this diary after the last blood draw.

Blood Draws for Pharmacokinetics (PK) Testing:

While you are on study, blood (about 1 teaspoon each time) will be drawn for PK testing. PK testing measures the amount of study drug in the body at different time points.

- Days 1, 3, and 10, before your first dose of study drug and 3, 5, and 10 hours after

the first dose of the day

- Days 2, 4, and 11, about 24 hours after the first dose the day before

Blood (about 1 teaspoon) will also be drawn for PK testing 1 time at any of the following time points:

- Before you start a new dose of study drug, if the dose needs to be raised

- If you stop taking the study drug due to intolerable side effects or a fungal infection

Note that if you are not already in the hospital on the days of the PK blood draws, you will need to stay at the hospital for about 10 hours on these days.

Length of the Study:

You will take the study drug for up to 42 days. You will be taken off study if you experience intolerable side effects, if you develop an invasive fungal infection, or if the doctor thinks it is in your best interest.

Additional Information:

You must not take certain drugs while you are on study. Your doctor will give you a list of drugs that you must avoid while on study. While on study, you must not take cyclosporine, sirolimus, tacrolimus, rifabutin, midazolam, phenytoin, atazanavir, or ritonavir.

This is an investigational study. Posaconazole is FDA approved and commercially available for the prevention of fungal infections.

Up to 25 patients will take part in the study. All will be enrolled at M. D. Anderson.

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

Criteria:

Inclusion Criteria:

1. Patients with diagnosis of refractory or relapsed AML or high-risk MDS who will receive first salvage chemotherapy. (Salvage patients are defined as patients that achieved remission and relapsed or patients who were refractory to initial frontline chemotherapy)

2. Age > 18 years and able to take oral intake.

3. Patients must sign an informed consent.

4. Patients agree to medically approved forms of contraception

5. Patients on prior antifungal prophylaxis with voriconazole, itraconazole or fluconazole are eligible if they completed 3 days wash-out period if on voriconazole, or 14 days wash-out period if on itraconazole or 7 days wash-out period if on fluconazole

Exclusion Criteria:

1. Patients with history of anaphylaxis attributed to azole compounds

2. Patients with clinical or other evidence that indicates that they have proven or probable invasive fungal infection prior to enrollment (EORTC criteria)

3. Patients with baseline total bilirubin levels > 3 times the upper normal limits (i. e. > 3. 0 mg/dl); or baseline SGPT > 5 times upper limit normal.

4. Patients receiving any medication that is contraindicated with the use of posaconazole

5. Patients with baseline creatinine levels NCI grade 3 or above (> 3. 0 - 6. 0 X ULN)

6. Patients with baseline QTc prolongation NCI grade 1 or above (QTc > 0. 45 - 0. 47

seconds).

7. Patients receiving CYP3A4 substrates, such as terfenadine, astemizole, cisapride, pimozide, halofantrine, or quinidine. A complete listing can be found at: ctep. cancer. gov/protocolDevelopment/docs/cyp3a4. doc

8. Patients receiving rifabutin, phenytoin, cimetidine and efavirenz, which may lower posaconazole plasma concentrations levels.

Jorge Cortes, MD, Phone: 713-745-2723

UT MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Jorge Cortes, MD, Principal Investigator

UT MD Anderson Cancer Center website

Starting date: September 2009
Last updated: October 2, 2009