Repeat Dose Safety Study for Compound to Treat Hematologic Cancer

Hematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00881946
• Other study ID #: PKB112835
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 20, 2009
• Last updated: April 3, 2012
• Start date: July 2009
• Est. completion date: March 2012

Study information

• Verified date: April 2012
• Source: Accenture
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hematologic Malignancies
• Neoplasms

Intervention

Drug:
• GSK21110183
Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Prince of Wales Hospital	Sydney	New South Wales
Canada	Princess Margaret Hospital	Toronto	Ontario
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Accenture

Countries where clinical trial is conducted

Australia,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Physical exam		Screening, Days -3, 8, At the start of each additional Cycle	Yes
Primary	Electrocardiogram (ECG)		Days -3, -2, -1, 8, 15, At the start of each additional Cycle	Yes
Primary	Vital signs		Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle	Yes
Primary	Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans		Screening, Additionally as needed	Yes
Primary	Clinical Laboratory assessments		Screening, Days -3, 1, 8, 15, At the start of each additional Cycle	Yes
Primary	ECOG Peformance Status		Screening, Days -3, 8, At the start of each additional Cycle	Yes
Primary	PK - Maximum observed plasma concentraion (Cmax)		Days -3, -2, -1, 8, 15	No
Primary	PK - time to Cmax [tmax] (Maximum observed plasma concentration)		Days -3, -2, -1, 8, 15	No
Primary	PK - Area under the plasma concentration-time curve (AUC(0-t))		Days -3, -2, -1, 8, 15	No
Primary	PK - Apparent terminal phase elimination rate constant		Days -3, -2, -1, 8, 15	No
Primary	PK - Apparent terminal phase half-life (t1/2)		Days -3, -2, -1, 8, 15	No
Primary	PK - oral clearance (CL/F)		Days -3, -2, -1, 8, 15	No
Secondary	Metabolite Profiling		Days -3, 8	No