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The purpose of this study is to characterize the safety and tolerability of repeat doses of compound GSK2110183 in subjects with hematologic cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2119183 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK21110183 | Drug | Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops |
|
| Measure | Description | Time Frame |
|---|---|---|
| Physical exam | Screening, Days -3, 8, At the start of each additional Cycle | |
| Electrocardiogram (ECG) | Days -3, -2, -1, 8, 15, At the start of each additional Cycle | |
| Vital signs | Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle | |
| Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans | Screening, Additionally as needed | |
| Clinical Laboratory assessments | Screening, Days -3, 1, 8, 15, At the start of each additional Cycle | |
| ECOG Peformance Status | Screening, Days -3, 8, At the start of each additional Cycle | |
| PK - Maximum observed plasma concentraion (Cmax) | Days -3, -2, -1, 8, 15 | |
| PK - time to Cmax [tmax] (Maximum observed plasma concentration) | Days -3, -2, -1, 8, 15 | |
| PK - Area under the plasma concentration-time curve (AUC(0-t)) | Days -3, -2, -1, 8, 15 | |
| PK - Apparent terminal phase elimination rate constant | Days -3, -2, -1, 8, 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolite Profiling | Days -3, 8 |
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Inclusion Criteria:
Written informed consent is provided.
Male or female who is at least 18 years of age or older.
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:
Performance Status score of 0 and 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
Able to swallow and retain oral medication.
Fasting serum glucose < 126 mg/dL (<7 mmol/L).
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.
A female subject is eligible to participate if she is of:
Adequate organ system function
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| S. Jamie Freedman, MD, PhD | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Prince of Wales Hospital | Sydney | New South Wales | 2031 | Australia | ||
| The Alfred Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25075128 | Derived | Spencer A, Yoon SS, Harrison SJ, Morris SR, Smith DA, Brigandi RA, Gauvin J, Kumar R, Opalinska JB, Chen C. The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014 Oct 2;124(14):2190-5. doi: 10.1182/blood-2014-03-559963. Epub 2014 Jul 29. |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D006689 | Hodgkin Disease |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D009101 | Multiple Myeloma |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| PK - Apparent terminal phase half-life (t1/2) | Days -3, -2, -1, 8, 15 |
| PK - oral clearance (CL/F) | Days -3, -2, -1, 8, 15 |
| Melbourne |
| Victoria |
| 3004 |
| Australia |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Seoul National University Hospital | Seoul | 110-744 | South Korea |
| D015448 |
| Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008223 | Lymphoma |
| D007951 | Leukemia, Myeloid |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |