Phase II Study of the Pharmacokinetics of Posaconazole Prophylaxis in Relapsed or Refractory Patients With Acute Leukemia
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Maximum Observed Concentration in Plasma (Cmax)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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).
Arms & Interventions
Posaconazole
Posaconazole 200 mg (liquid) by mouth 3 times per day.
Intervention: Posaconazole (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
No secondary outcomes reported