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LeukemiaPhase 1/2NCT01752426

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 Phase 1/2 study testing Heavy Water (2H2O) and PCI-32765 in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Heavy Water (2H2O) and PCI-32765
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
17 Dec 2012to 9 Aug 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A diagnosis of CLL/ SLL and have not been previously treated.
  • An indication for treatment by 2008 IWCLL Criteria.
  • Male and female subjects of age >/= 18 years at the time of signing informed consent and requiring treatment within the next 2 to 6 months.
  • Understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations.
  • Platelet counts at study entry must be greater than 50,000/µL and absolute neutrophil counts at study entry must be greater than 750/µL.
  • Free of prior malignancies for 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast.
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  • Subjects must be able to contribute the required amount of blood and/or tissue without compromising their well-being or care and must weigh at least 110 pounds.
  • Adequate renal and hepatic function as indicated by all of the following: total bilirubin </=1.5 x institutional Upper Limit of Normal (ULN); Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) </=2.5 x Upper limits of normal (ULN); and estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the Cockcroft-Gault equation.
  • Participants must be willing to be contacted again for consideration of additional studies in the future, such as a blood draw or another action (e.g., bone marrow aspiration and/or biopsy) that would be associated with their standard of care, unless they consented to such for research purposes.
  • An Eastern Cooperative Oncology (ECOG)/World Health Organization (WHO) performance status of 0-2.
  • Males and females of child bearing potential must have adequate birth control protection while on study and for 30 days after the last dose of study drug. The couple will use two forms of birth control for the entire time of the study and 30 days after finishing study. Conception control should include a hormonal method (birth control pill, etc.), and a double-barrier methods (condoms with spermicidal, sponge with spermicidal, or diaphragm with spermicidal), or abstinence (not having sex) will be practiced.
  • Female subjects will need a negative pregnancy screening test if they are of child bearing potential.

Who cannot join

  • Subjects less than 18 years of age.
  • A lymphocyte doubling time of < 3 months, or other clinical or laboratory signs indicating that a treatment delay of 2 months or longer (due to heavy water labeling and resting period) would result in a significant progression of the disease and be detrimental to the subject, as determined by the treating physician.
  • Any prior treatment for Chronic Lymphocytic Leukemia (CLL) including chemotherapy, chemoimmunotherapy, monoclonal antibody therapy, radiotherapy, or high-dose corticosteroid therapy (Prednisone > 60 mg daily or equivalent), or immunotherapy prior to enrollment or concurrent with this trial.
  • Concomitant use of agents that have been described to affect the biology and/or proliferation rate of CLL cells such as: Phosphodiesterase inhibitors (PDE-inhibitors) (e.g., sildenafil, theophylline), immunosuppressive agents (e.g., prednisone, cyclosporin-A, rapamycin), green tea extract, itraconazole, ketoconazole, clarithromycin, bupropion, and Cox-2 inhibitors.
  • Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
  • Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
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  • Subjects with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP).
  • Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the subject at undue risk to undergo therapy with PCI-32765.
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study.
  • History of intracranial hemorrhage or stroke within 6 months prior to the study.
  • Evidence of bleeding diathesis or coagulopathy.
  • Major surgical procedure, open biopsy, or significant traumatic injury, within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study. (Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1. Bone marrow aspiration +/- biopsy is allowed).
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Subjects receiving anticoagulation (for example heparin, Coumadin, low-molecular-weight heparin (LMWH, such as Lovenox), and anti-platelet drugs (except for low-dose aspirin) will be ineligible to participate in this study. Subjects who recently received drugs for anticoagulation must be off those medications for at least 7 days prior to start of the study.
  • Subjects who are known to be anemic, with hemoglobin <8.0g/dl.
  • Weight less than 110 pounds
  • Subjects who are known to be infected with HIV, or have signs of active Hepatitis B or Hepatitis C.
  • Biliary obstruction, acute hepatitis, severe liver failure, or severely impaired renal function.
  • PCI-32765 is contraindicated in subjects with clinically significant hypersensitivity to any of the compound's structural components.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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)

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.

Read the detailed description

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.

Conditions
Leukemia
Being tested
Heavy Water (2H2O), PCI-32765
Keywords
Leukemia, Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL, PCI-32765, Ibrutinib, Btk inhibitor, Heavy water, 2H2O
Medical subject headings
Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Heavy Water (2H2O)Other

    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.

  • PCI-32765Drug

    Also called Ibrutinib

    420 mg orally once daily.

Study groups in NCT01752426
Study groupRoleWhat they receive
Heavy Water + PCI-32765ExperimentalSubjects 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.
Receives: Other: Heavy Water (2H2O); Drug: PCI-32765

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Leukemia Cell Death

    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 .

    Measured: every three months, up to one year

Secondary outcomes (1)

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

    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.

    Measured: every three months, up to one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2012 (estimated)
  2. Study start17 Dec 2012
  3. Primary completion9 Aug 2018
  4. Study completion9 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01752426
Sponsor's protocol ID
2012-0086
Other IDs
NCI-2013-00029
Status last verified
Feb 2020
First submitted
13 Dec 2012
Last updated
24 Feb 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Kim E, Chen SS, Sivina M, Hwang H, Huang X, Ferrajoli A, Jain N, Wierda WG, Wodarz D, Chiorazzi N, Burger JA. Deuterated water labeling in ibrutinib-treated patients with CLL: leukemia cell kinetics correlate with IGHV, ZAP-70, and MRD. Blood. 2024 Dec 19;144(25):2678-2681. doi: 10.1182/blood.2024025683.

    PubMed 39441901

  • Burger JA, Li KW, Keating MJ, Sivina M, Amer AM, Garg N, Ferrajoli A, Huang X, Kantarjian H, Wierda WG, O'Brien S, Hellerstein MK, Turner SM, Emson CL, Chen SS, Yan XJ, Wodarz D, Chiorazzi N. Leukemia cell proliferation and death in chronic lymphocytic leukemia patients on therapy with the BTK inhibitor ibrutinib. JCI Insight. 2017 Jan 26;2(2):e89904. doi: 10.1172/jci.insight.89904.

    PubMed 28138560

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Heavy Water (2H2O) and PCI-32765 in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Leukemia Cell Death (time frame: every three months, up to one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01752426, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2020.

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