Pharmacokinetics of Posaconazole Prophylaxis in Acute Leukemia

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ClinicalTrials.gov Identifier: NCT00936117

Recruitment Status : Completed

First Posted : July 9, 2009

Results First Posted : September 24, 2015

Last Update Posted : February 27, 2019

Sponsor:

Collaborator:

Schering-Plough

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia Fungal Infection	Drug: Posaconazole	Phase 2

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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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	25 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Study of the Pharmacokinetics of Posaconazole Prophylaxis in Relapsed or Refractory Patients With Acute Leukemia
Study Start Date :	September 2009
Actual Primary Completion Date :	September 2013
Actual Study Completion Date :	September 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Drug Information available for: Posaconazole

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Posaconazole Posaconazole 200 mg (liquid) by mouth 3 times per day.	Drug: Posaconazole 200 mg (liquid) by mouth 3 times per day. Other Names: SCH 56592 Noxafil

Outcome Measures

Primary Outcome Measures :

Maximum Observed Concentration in Plasma (Cmax) [ Time Frame: Pharmacokinetics: Day 1, Day 3 and Day 10 of prophylaxis. ]
Pharmacokinetic samples were obtained on day 1, day 3 and day 10 of prophylaxis. A total of 15 samples (3 ml each sample) per participant were obtained, with thrice daily dosing planned around standard meal times. On day 1 and day 3 of prophylaxis sampling was done pre dose (0), and at 3, 5, 10 and 24 hours (±10 minutes) post dose from the time of the first dose of the day. On day 10 of prophylaxis sampling was done pre dose (0), and at 3, 5, and 10 hours (±10 minutes) post dose from the time of the first dose of the day.

Posaconazole levels were assayed by high performance liquid chromatography (HPLC). The testing range for posaconazole is from 125 - 5000 ng/ml. There are no established therapeutic ranges for posaconazole.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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)
Age > 18 years and able to take oral intake.
Patients must sign an informed consent.
Patients agree to medically approved forms of contraception
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:

Patients with history of anaphylaxis attributed to azole compounds
Patients with clinical or other evidence that indicates that they have proven or probable invasive fungal infection prior to enrollment (EORTC criteria)
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.
Patients receiving any medication that is contraindicated with the use of posaconazole
Patients with baseline creatinine levels NCI grade 3 or above (> 3.0 - 6.0 X ULN)
Patients with baseline QTc prolongation NCI grade 1 or above (QTc > 0.45 - 0.47 seconds).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00936117

Locations

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United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Schering-Plough

Investigators

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Study Chair:	Jorge Cortes, MD	UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

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Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00936117
Other Study ID Numbers:	2008-0793
First Posted:	July 9, 2009 Key Record Dates
Results First Posted:	September 24, 2015
Last Update Posted:	February 27, 2019
Last Verified:	February 2019

Keywords provided by M.D. Anderson Cancer Center:


Cancer of the Blood Cancer of Bone Marrow Acute Leukemia AML Fungal infection	Prophylaxis Posaconazole SCH 56592 Noxafil Chemotherapy

Additional relevant MeSH terms:

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Mycoses Leukemia Neoplasms by Histologic Type Neoplasms Infections Bacterial Infections and Mycoses Posaconazole Antifungal Agents Anti-Infective Agents Trypanocidal Agents	Antiprotozoal Agents Antiparasitic Agents 14-alpha Demethylase Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Steroid Synthesis Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs

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