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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pharmacyclics
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01752426
First received: December 13, 2012
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Other: Heavy Water (2H2O)
Drug: PCI-32765
Phase 1
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 30
Study Start Date: December 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A diagnosis of CLL/ SLL and have not been previously treated.
  2. An indication for treatment by 2008 IWCLL Criteria.
  3. 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.
  4. Understand and voluntarily sign an informed consent, and be able to comply with study procedures and follow-up examinations.
  5. 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.
  6. 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.
  7. 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.
  8. Adequate renal and hepatic function as indicated by all of the following: total bilirubin </=1.5 x institutional Upper Limit of Normal (ULN); AST or ALT </=2.5 x ULN; and estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the Cockcroft-Gault equation.
  9. 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.
  10. An ECOG/WHO performance status of 0-2.
  11. 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.
  12. Female subjects will need a negative pregnancy screening test if they are of child bearing potential.

Exclusion Criteria:

  1. Subjects less than 18 years of age.
  2. 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.
  3. Any prior treatment for 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.
  4. Concomitant use of agents that have been described to affect the biology and/or proliferation rate of CLL cells such as: 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.
  5. 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.
  6. 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).
  7. Subjects with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune thrombocytopenia (ITP).
  8. 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.
  9. 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.
  10. History of intracranial hemorrhage or stroke within 6 months prior to the study.
  11. Evidence of bleeding diathesis or coagulopathy.
  12. 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).
  13. Serious, non-healing wound, ulcer, or bone fracture.
  14. 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.
  15. Subjects who are known to be anemic, with hemoglobin <8.0g/dl.
  16. Weight less than 110 pounds
  17. Subjects who are known to be infected with HIV, or have signs of active Hepatitis B or Hepatitis C.
  18. Biliary obstruction, acute hepatitis, severe liver failure, or severely impaired renal function.
  19. PCI-32765 is contraindicated in subjects with clinically significant hypersensitivity to any of the compound's structural components.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01752426

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pharmacyclics
Investigators
Principal Investigator: Jan A. Burger, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01752426     History of Changes
Other Study ID Numbers: 2012-0086, NCI-2013-00029
Study First Received: December 13, 2012
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Chronic Lymphocytic Leukemia
CLL
Small Lymphocytic Lymphoma
SLL
PCI-32765
Ibrutinib
Btk inhibitor
Heavy water
2H2O

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Deuterium Oxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014