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Leukemia, Lymphoid

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Antineoplastic Agents

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Ibrutinib

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Tyrosine

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.

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.

Heavy Water (2H2O)

PCI-32765

Jan A. Burger, MD

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.

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 Visi:

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 FDA approved and commercially available for the treatment of patients with mantle cell lymphoma. Its use in this study is investigational.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

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

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)

Stable isotopic labeling with deuterated water (2\^H2O) to measure directly the effects of PCI-32765 (ibrutinib) on leukemia cell death in the peripheral blood of participants .

Measurement of the fraction of recently born versus older leukemia cells in the peripheral blood of participants before and during PCI-32765 therapy, to determine the effects of PCI-32765 (ibrutinib) therapy on the birth rates of the leukemia cells.

Pharmacyclics LLC.

M.D. Anderson Cancer Center

50ml 70% 2\^H2O (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 2\^H2O to consume at home; after the 5-day loading period, a 60 ml maintenance dose of 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (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.

Heavy Water (2\^H2O): 50 ml 70% 2\^H2O 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 2\^H2O will be drunk at bedtime. At end of the 4th week, subjects stop drinking 2\^H2O (washout phase) and be followed from 6-12

Heavy Water + PCI-32765

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Jan Burger MD./Professor

Daily death rate of blood cells before therapy

Daily death rate of blood cells after therapy

Change in Leukemia Cell Death

Daily cell birth rate before therapy

Daily cell birth rate during therapy

Percentage of Recently Born Leukemia Cells Mobilized Into the Blood by PCI-32765 Treatment

Overall Study

Spots Global Cancer Trial Database for heavy water (2h2o)