Hematologic MalignanciesPhase 1/2NCT00881946
Repeat Dose Safety Study for Compound to Treat Hematologic Cancer
A Phase 1/2 study testing GSK21110183 in people with Hematologic Malignancies, run by Accenture at 4 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- GSK21110183
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Jul 2009to Mar 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- 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:
- chronic lymphocytic leukemia (CLL),
- chronic myelogenous leukemia (CML),
- multiple myeloma (MM),
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- 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
- 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:
- 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.
- Adequate organ system function
Who cannot join
- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of study drug.
- Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
- Current use of a prohibited medication or requires any of these medications during treatment with study drug.
- 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.
- Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than aspirin (81 mg daily).
- Presence of active gastrointestinal disease or other condition that could affect gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to gastrointestinal ulceration.
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- Any major surgery within the last four weeks.
- Unresolved toxicity (except alopecia) Grade 2 from previous anti-cancer therapy unless agreed to by a Medical Monitor and the Investigator
- Previously diagnosed diabetes mellitus (Type 1 or 2).
- Current use of oral corticosteroids, with the exception of inhaled or topical corticosteroids.
- 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.
- Symptomatic or untreated central nervous system (CNS) involvement by the hematologic malignancy (including primary CNS lymphoma).
- Evidence of severe or uncontrolled systemic diseases
- Known infection with HIV, HBV or HCV.
- QTc interval ≥ 470 msecs.
- Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within the past six months.
- Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Pregnant or lactating female.
- Active drug or alcohol abuse.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Australia2 sites
The Alfred Hospital
Melbourne, Victoria, 3004
Prince of Wales Hospital
Sydney, New South Wales, 2031
About this study
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
The purpose of this study is to characterize the safety and tolerability of repeat doses of compound GSK2110183 in subjects with hematologic cancer.
- Conditions
- Hematologic Malignancies
- Being tested
- GSK21110183
- Keywords
- chronic lymphocytic leukemia, aggressive lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, chronic myelogenous leukemia, multiple myeloma, acute lymphoblastic leukemia, acute myeloid leukemia
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Hodgkin Disease, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Multiple Myeloma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK21110183Drug
Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops
| Study group | Role | What they receive |
|---|---|---|
| GSK2119183 | Experimental | Not described Receives: Drug: GSK21110183 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physical exam
Measured: Screening, Days -3, 8, At the start of each additional Cycle
Electrocardiogram (ECG)
Measured: Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Vital signs
Measured: Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans
Measured: Screening, Additionally as needed
Clinical Laboratory assessments
Measured: Screening, Days -3, 1, 8, 15, At the start of each additional Cycle
ECOG Peformance Status
Measured: Screening, Days -3, 8, At the start of each additional Cycle
PK - Maximum observed plasma concentraion (Cmax)
Measured: Days -3, -2, -1, 8, 15
PK - time to Cmax [tmax] (Maximum observed plasma concentration)
Measured: Days -3, -2, -1, 8, 15
PK - Area under the plasma concentration-time curve (AUC(0-t))
Measured: Days -3, -2, -1, 8, 15
PK - Apparent terminal phase elimination rate constant
Measured: Days -3, -2, -1, 8, 15
PK - Apparent terminal phase half-life (t1/2)
Measured: Days -3, -2, -1, 8, 15
PK - oral clearance (CL/F)
Measured: Days -3, -2, -1, 8, 15
Secondary outcomes (1)
Metabolite Profiling
Measured: Days -3, 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2009 (estimated)
- Study startJul 2009
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Accenture
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- S. Jamie Freedman, MD, PhD, Study director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00881946
- Sponsor's protocol ID
- PKB112835
- Status last verified
- Apr 2012
- First submitted
- 20 Mar 2009
- Last updated
- 4 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25075128
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00881946
- Acronym / sponsor ID
- PKB112835
- Conditions
- Hematologic Malignancies
- Keywords
- chronic lymphocytic leukemia, aggressive lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, chronic myelogenous leukemia, multiple myeloma, acute lymphoblastic leukemia, acute myeloid leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- AccentureIndustry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 15 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to characterize the safety and tolerability of repeat doses of compound GSK2110183 in subjects with hematologic cancer.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2119183 | Experimental | Drug: GSK21110183 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (21 listed)
- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of study drug.
- Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
- Current use of a prohibited medication or requires any of these medications during treatment with study drug.
- 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.
- Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than aspirin (81 mg daily).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK21110183Starting Dose = 25mg once daily with dose escalation until unacceptable toxicity develops | Drug | GSK2119183 |
Primary outcome
Physical exam
Time frame: Screening, Days -3, 8, At the start of each additional Cycle
Electrocardiogram (ECG)
Time frame: Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Vital signs
Time frame: Screening, Days -3, -2, -1, 8, 15, At the start of each additional Cycle
Transthoracic Echocardiogram (TTE)/Multiple Gated Acquisition (MUGA) Scans
Time frame: Screening, Additionally as needed
Clinical Laboratory assessments
Time frame: Screening, Days -3, 1, 8, 15, At the start of each additional Cycle
ECOG Peformance Status
Time frame: Screening, Days -3, 8, At the start of each additional Cycle
PK - Maximum observed plasma concentraion (Cmax)
Time frame: Days -3, -2, -1, 8, 15
PK - time to Cmax [tmax] (Maximum observed plasma concentration)
Time frame: Days -3, -2, -1, 8, 15
PK - Area under the plasma concentration-time curve (AUC(0-t))
Time frame: Days -3, -2, -1, 8, 15
PK - Apparent terminal phase elimination rate constant
Time frame: Days -3, -2, -1, 8, 15
PK - Apparent terminal phase half-life (t1/2)
Time frame: Days -3, -2, -1, 8, 15
PK - oral clearance (CL/F)
Time frame: Days -3, -2, -1, 8, 15
1 secondary outcome
Metabolite Profiling
Time frame: Days -3, 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2012.
- Derived from this study: PubMed 25075128Spencer 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
S. Jamie Freedman, MD, PhD study director
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GSK21110183 in people with Hematologic Malignancies, run by Accenture at 4 sites in 3 countries.
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 21 inclusion and 21 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 4 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, Canada, South Korea. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Physical exam (time frame: Screening, Days -3, 8, At the start of each additional Cycle). The study lists 12 primary outcomes in all. 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 NCT00881946, which also lists 1 linked publication.
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 4 Apr 2012.