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Repeat Dose Safety Study for Compound to Treat Hematologic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00881946
Recruitment Status : Completed
First Posted : April 15, 2009
Last Update Posted : April 4, 2012
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to characterize the safety and tolerability of repeat doses of compound GSK2110183 in subjects with hematologic cancer.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Drug: GSK21110183 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 73 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase I, Open-Label, Two-Stage Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral AKT Inhibitor GSK2110183 in Subjects With Any Hematologic Malignancy
Study Start Date : July 2009
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: GSK2119183 Drug: GSK21110183
Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops

Primary Outcome Measures :
  1. Physical exam [ Time Frame: Screening, Days -3, 8, At the start of each additional Cycle ]
  2. Electrocardiogram (ECG) [ Time Frame: Days -3, -2, -1, 8, 15, At the start of each additional Cycle ]
  3. Vital signs [ Time Frame: Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle ]
  4. Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans [ Time Frame: Screening, Additionally as needed ]
  5. Clinical Laboratory assessments [ Time Frame: Screening, Days -3, 1, 8, 15, At the start of each additional Cycle ]
  6. ECOG Peformance Status [ Time Frame: Screening, Days -3, 8, At the start of each additional Cycle ]
  7. PK - Maximum observed plasma concentraion (Cmax) [ Time Frame: Days -3, -2, -1, 8, 15 ]
  8. PK - time to Cmax [tmax] (Maximum observed plasma concentration) [ Time Frame: Days -3, -2, -1, 8, 15 ]
  9. PK - Area under the plasma concentration-time curve (AUC(0-t)) [ Time Frame: Days -3, -2, -1, 8, 15 ]
  10. PK - Apparent terminal phase elimination rate constant [ Time Frame: Days -3, -2, -1, 8, 15 ]
  11. PK - Apparent terminal phase half-life (t1/2) [ Time Frame: Days -3, -2, -1, 8, 15 ]
  12. PK - oral clearance (CL/F) [ Time Frame: Days -3, -2, -1, 8, 15 ]

Secondary Outcome Measures :
  1. Metabolite Profiling [ Time Frame: Days -3, 8 ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent is provided.
  2. Male or female who is at least 18 years of age or older.
  3. Histologically- or cytologically-confirmed diagnosis of a hematologic malignancy - that has relapsed or is refractory after standard therapy, AND that is not associated with human immunodeficiency virus (HIV) infection or solid organ transplant, including:

    • chronic lymphocytic leukemia (CLL),
    • chronic myelogenous leukemia (CML),
    • multiple myeloma (MM),
    • non-Hodgkin's lymphoma (NHL),
    • Hodgkin's lymphoma, or
    • Other hematologic malignancy excluding:
    • acute leukemia of any type
    • CML blast crisis
    • myelodysplastic syndrome (MDS)
    • myelofibrosis
  4. Performance Status score of 0 and 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
  5. Able to swallow and retain oral medication.
  6. Fasting serum glucose < 126 mg/dL (<7 mmol/L).
  7. Male subjects with a female partner of childbearing potential must have had a prior vasectomy or agree to use adequate contraception from the time of the first dose of study drug until three months after the last dose of study drug.
  8. A female subject is eligible to participate if she is of:

    • Non-childbearing potential
    • Child-bearing potential, has a negative serum pregnancy test during the screening period, and agrees to use adequate contraception from screening until four weeks after the last dose of study drug.
  9. Adequate organ system function

Exclusion Criteria:

  1. Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of study drug.
  2. Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
  3. Current use of a prohibited medication or requires any of these medications during treatment with study drug.
  4. Current use of anticoagulants at therapeutic levels within seven days prior to the first dose of study drug, including warfarin, low molecular weight heparin and direct thrombin inhibitors. Low dose (prophylactic) anticoagulants are permitted provided that subject's PT and PTT meet entry criteria.
  5. Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than aspirin (81 mg daily).
  6. Presence of active gastrointestinal disease or other condition that could affect gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to gastrointestinal ulceration.
  7. Any major surgery within the last four weeks.
  8. Unresolved toxicity (except alopecia) Grade 2 from previous anti-cancer therapy unless agreed to by a Medical Monitor and the Investigator
  9. Previously diagnosed diabetes mellitus (Type 1 or 2).
  10. Current use of oral corticosteroids, with the exception of inhaled or topical corticosteroids.
  11. Any serious or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or with obtaining informed consent.
  12. Symptomatic or untreated central nervous system (CNS) involvement by the hematologic malignancy (including primary CNS lymphoma).
  13. Evidence of severe or uncontrolled systemic diseases
  14. Known infection with HIV, HBV or HCV.
  15. QTc interval ≥ 470 msecs.
  16. Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
  17. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within the past six months.
  18. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  19. Pregnant or lactating female.
  20. Active drug or alcohol abuse.
  21. History of sensitivity to heparin or heparin-induced thrombocytopenia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00881946

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Australia, New South Wales
Prince of Wales Hospital
Sydney, New South Wales, Australia, 2031
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
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Study Director: S. Jamie Freedman, MD, PhD

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Accenture Identifier: NCT00881946    
Other Study ID Numbers: PKB112835
First Posted: April 15, 2009    Key Record Dates
Last Update Posted: April 4, 2012
Last Verified: April 2012
Keywords provided by Accenture:
chronic lymphocytic leukemia
aggressive lymphoma
non-Hodgkin's lymphoma
Hodgkin's lymphoma
chronic myelogenous leukemia
multiple myeloma
acute lymphoblastic leukemia
acute myeloid leukemia
Additional relevant MeSH terms:
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