Clinical trial NCT00936117: Pharmacokinetics of Posaconazole Prophylaxis in Acute Leukemia
Official title: Phase II Study of the Pharmacokinetics of Posaconazole Prophylaxis in Relapsed or Refractory Patients With Acute Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Fungal Infection
Keywords: Cancer of the Blood
Cancer of Bone Marrow
Acute Leukemia
AML
Fungal infection
Prophylaxis
Posaconazole
SCH 56592
Noxafil
Chemotherapy
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2009-07-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Objectives:

Primary:

To study the plasma pharmacokinetics of posaconazole in patients with newly diagnosed acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS) undergoing induction chemotherapy or relapsed or refractory patients who will receive salvage chemotherapy.

Secondary:

To evaluate the safety of posaconazole given as prophylaxis.

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.

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 and 4, 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.

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 MD Anderson.

Eligibility criteria: Inclusion Criteria:

1. Patients newly diagnosed with AML or high-risk MDS undergoing induction chemotherapy or refractory or relapsed patients with AML or high-risk MDS who will receive first or second 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).

Primary outcomes:
measure: Maximum Observed Concentration in Plasma (Cmax)
timeFrame: Pharmacokinetics: Day 1, Day 3 and Day 10 of prophylaxis.
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: UT MD Anderson Cancer Center
name: Jorge Cortes, MD
role: STUDY_CHAIR
References: