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)
Heavy Water Administration:
If you are found to be eligible to take part in this study, you will receive heavy water to
drink for 4 weeks. The vials of heavy water will be shipped to your home location.
On Days 1-5, you will drink the heavy water 3 times each day. You will drink 1 dose in the
morning, 1 dose in the afternoon, and 1 dose in the evening. You should take the doses at
least 3 hours apart. If you miss a dose, take it as soon as you remember. Make sure to wait
at least 3 hours between doses.
Starting on Day 6 and until your first study visit, you will drink the heavy water 1 time
each day in the evening.
You may choose to drink the heavy water with or without food.
You will be given a study diary to record your doses. If you miss a dose, take it as soon as
you remember. If you vomit a dose, you do not need to make it up. Just wait until the next
regularly scheduled dose and make a note of it in the diary.
Heavy Water Study Visits:
On Day 1 and during Weeks 2 and 4, blood (about 5 tablespoons) will be drawn for routine
tests and for heavy water testing. These blood samples will not be banked for future
research. The samples will only be used for research in this study and will be kept until
all DNA and protein analysis is complete. These Samples will be sent to our collaborators at
the Feinstein Institute for Medical Research and KineMed, Inc., in order to conduct the
heavy water analyses.
After Week 4, you will stop drinking the heavy water and will be followed either in the
clinic or by your local doctor for 6-12 weeks.
Every 2 weeks during the time after you stop drinking heavy water and before you start
taking ibrutinib, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 4 tablespoons) will be drawn for heavy water testing. This measures how
fast the cancer cells are making new protein and DNA.
- You will be asked about any drugs you may be taking.
Every 4 weeks during the time after you stop drinking heavy water and before you start
taking ibrutinib, blood (about 1 tablespoon) will be drawn for routine tests.
Ibrutinib Administration:
Beginning around Weeks 10-16, you will start taking ibrutinib. You will take 3 capsules by
mouth with 1 cup (8 ounces) of water 1 time a day. The dose should be taken at least 30
minutes before eating and at least 2 hours after a meal, at about the same time each day.
If you miss or vomit a dose, do not make up the dose. Take the next dose at your regularly
scheduled time and be sure to write it down in the study diary.
You will take the study drug for up to 12 cycles. Each cycle is 28 days. If the doctor
thinks it is in your best interest, you may continue taking the study drug even after 12
cycles.
You will also take allopurinol by mouth 1 time each day during the first 1-2 weeks of taking
ibrutinib to lower the risk of side effects.
Ibrutinib Study Visits:
At every study visit, you will be asked about any drugs you may be taking and about any side
effects you may be having.
On Days 1 and 3 of Week 1, and at the end of Weeks 2, 4, 6, 8, and 10:
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Blood (about 4 tablespoons) will be drawn for heavy water testing.
At the end of Week 12:
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Blood (about 4 tablespoons) will be drawn for heavy water testing.
- You will have computed tomography (CT) scans of the chest, abdomen, and pelvis to check
the status of the disease.
- You will have a bone marrow aspiration to check the status of the disease. To collect a
bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a
small amount of bone marrow is withdrawn through a large needle.
At the end of Weeks 16 and 20:
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 tablespoon) will be drawn for routine tests.
At the end of Weeks 24 and 36:
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have CT scans to check the status of the disease.
- You will have a bone marrow aspiration to check the status of the disease.
At the end of Week 48:
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have CT scans to check the status of the disease.
Length of Study Drug Dosing:
You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the end-of-study visits.
Follow-Up Visits:
If you continue taking the study drug past 12 cycles, you will come to the clinic for
follow-up visits every month. You will continue to have follow-up visits as long as you are
taking the study drug. At each visit, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of you vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
Whenever the doctor thinks it is needed, you will have the following tests and procedures:
- You may have CT scans to check the status of the disease.
- You may have a bone marrow aspiration to check the status of the disease.
End-of-Study Visits:
After your last dose of study drug, and then 1 more time during the next month, you will
have end-of-study visits. The following tests and procedures will be performed:
- You will have a physical exam, including measurement of you vital signs.
- You will be asked about any symptoms you may be having.
- Blood (about 1 tablespoon) will be drawn for routine tests.
This is an investigational study. Ibrutinib is not commercially available or FDA approved.
It is currently being used for research purposes only.
Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Impact of PCI-32765 on Leukemia Cell Trafficking and Death
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.
12 weeks
No
Jan A. Burger, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2012-0086
NCT01752426
December 2012
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |