Pilot Study to Determine Effects of the Btk Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With CLL and SLL
The goal of this clinical research study is to learn how PCI-32765 (ibrutinib) may affect the life cycle of blood-cancer cells. Cancer cells will be "labeled" with heavy water to learn about their birth rates and death rates.
Ibrutinib is a type of drug called a kinase inhibitor. Kinases are proteins inside cells that help cells live and grow. The study drug is designed to inhibit or "block" the activity of a type of kinase that helps blood-cancer cells live and grow. By blocking the activity of this specific kinase, it is possible that the study drug may kill the cancer cells or stop them from growing.
Heavy water (2H2O) is a special type of water that is designed to help researchers learn how quickly cancer cells in the body reproduce.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study to Determine the Effects of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 on Leukemia Cell Kinetics and Trafficking, Using Heavy Water Labeling in Subjects With Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)|
- Impact of PCI-32765 on Leukemia Cell Trafficking and Death [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Statistical analysis is characterization of pattern of labeled cells (LC) over time. Patterns analyzed both visually and using more formal statistical methods in an exploratory manner. First, pattern will be smoothed using a cubic spline interpolation (SAS Graph, SAS Institute, Cary, NC). This will facilitate the determination of shape and numbers and patterns of peaks by eliminating "noise" in the data. Second, based on the patterns observed after smoothing, the data will be fit to candidate regression models (e.g., parabolas, mixtures of parabolas, piecewise curves, etc.) and the best fitting model will be identified using common statistical methods such as R2, Akaike's information, etc. All curves will be fit on individual subjects, thereby permitting subjects to vary in the pattern of their LC response curves.
|Study Start Date:||December 2012|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Heavy Water + PCI-32765
Subjects given 50ml 70% 2H2O (Heavy Water) 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks (labeling phase). Subjects given first dose in clinic. Subjects then given individual doses of 2H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765. PCI-32765 administered with 8 ounces (~240mL) of water at a dose of 420 mg (3 x 140mg capsules) orally once daily and continued daily. Treatment duration is 12 cycles, with each cycle consisting of 28 days.
Other: Heavy Water (2H2O)
50 ml 70% 2H2O 3 times a day for the first 5 days followed by 60 ml daily for a total of 4 weeks. After the 5-day loading period, a 60 ml maintenance dose of 2H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2H2O (washout phase) and be followed from 6-12 weeks until beginning treatment with PCI-32765.Drug: PCI-32765
420 mg orally once daily.
Other Name: Ibrutinib
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|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jan A. Burger, MD||UT MD Anderson Cancer Center|