CancerPhase 2NCT00920140
Open-label Study to Evaluate the Safety, PK, and PD of MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias
A Phase 2 study testing GSK1120212 in people with Cancer, run by GlaxoSmithKline at 28 sites in 4 countries.
Trial summary
MEK111759 is a dose-escalation, Phase I/II, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 in subjects with relapsed or refractory leukemias. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- GSK1120212
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 28 sitesin 4 countries
- Study dates
- May 2011to Apr 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Phase I
- Written informed consent provided.
- 18 years old or older.
- Subjects must have relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Subjects with poor-risk myelodysplasia (MDS) and chronic melomonocytic leukemia (CMML) are also eligible. Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blast crisis. Subjects with agnogenic myeloid metaplasia (AMM) are also eligible. Subjects with a haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant are NOT eligible.
- Subjects who have previously received an autologous stem cell transplant are allowed if a minimum of three months has elapsed from the time of transplant (T0) and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK1120212.
- Subjects with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was greater than 100 days prior to study enrolment, subject has not taken immunosuppressive medications (per protocol) for at least 1 month, no signs or symptoms of graft versus host disease other than Grade 1 skin involvement, no active infection, subject meets the remainder of the eligibility criteria outlined in this protocol.
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- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
- Life expectancy of at least four weeks.
- Able to swallow and retain oral medication.
- Male subjects must agree to use one of the contraception methods listed in the protocol.
- Female subjects must be of non-childbearing potential as listed in the protocol or using a contraception method listed in the protocol.
- Calcium Phosphate Product less than or equal to 4.0 mmol (squared)/L (squared) or 50mg (squared)/dL (squared).
- Subjects must have adequate organ function as specified in the protocol.
- Phase II
- Confirmed diagnosis of one of the following: Relapsed or refractory acute myeloid leukemia (AML), Secondary AML including AML arising from antecedent hematologic diseases (e.g., myelodysplastic syndrome, myeloproliferative disorders, or therapyrelated AML), CMML, or MDS.
- Cohorts 1: RAS Positive AML/MDS Cohort 2: Wild Type AML/MDS/CMML Cohort 3: RAS Positive CMML
Who cannot join
- Phase I
- Currently receiving cancer therapy as specified in the protocol.
- Received corticosteroids or imatinib within 24h of GSK1120212 administration.
- Received gemtuzumab ozogamicin (myelotarg) within two weeks of GSK1120212 adminstration.
- Received an investigational anti-cancer drug within four weeks or five half-lives, whichever is shorter of GSK1120212 administration, as specified in the protocol.
- Received major surgery, radiotherapy, or immunotherapy within four weeks of GSK1120212 administration.
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- Received chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Received chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last two weeks.
- Received a MEK inhibitor.
- Current use of a prohibited medication per protocol.
- Current use of warfarin. Low molecular weight heparin and prophylactic low-dose warfarin are permitted per protocol.
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
- History of RVO.
- Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis.
- Intraocular pressure greater than 21mm Hg as measured by tonography.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Condition that in the investigator's opinion would jeopardize compliance with the protocol.
- Symptomatic or untreated central nervous system involvement by the hematologic malignancy, including primary CNS lymphoma. Subjects who were previously treated for CNS involvement, and are asymptomatic without anti-epileptic medications for at least two months are eligible.
- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).
- Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia (if applicable) unless agreed to by a GSK Medical Monitor and the investigator.
- QTc interval greater than 480 msecs.
- History of acute coronary syndromes (including unstable angina), coronary angioplasty or stenting within the past 24 weeks.
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, dimethyl sulfoxide (DMSO), or excipients (See Section 3.10). (To date there are no known FDA approved drugs chemically related to GSK1120212).
- Pregnant or lactating female.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial locations and contacts
28 sites in 4 countries.
28 sites in 4 countries
United States15 sites
GSK Investigational Site
Birmingham, Alabama, 35249
GSK Investigational Site
Bornx, New York, 10467
GSK Investigational Site
Chicago, Illinois, 60611
GSK Investigational Site
Duarte, California, 91010
GSK Investigational Site
Hershey, Pennsylvania, 17033
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Lake Success, New York, 11042
GSK Investigational Site
Los Angeles, California, 90095
GSK Investigational Site
New York, New York, 10032
GSK Investigational Site
Pittsburgh, Pennsylvania, 15232
GSK Investigational Site
Portland, Oregon, 97239
GSK Investigational Site
Rochester, Minnesota, 55905
GSK Investigational Site
San Francisco, California, 94143
GSK Investigational Site
Seattle, Washington, 98109-1023
GSK Investigational Site
Winston-Salem, North Carolina, 27157-1009
Germany6 sites
GSK Investigational Site
Dresden, Saxony, 01307
GSK Investigational Site
Duisburg, North Rhine-Westphalia, 47166
GSK Investigational Site
Frankfurt am Main, Hesse, 60590
GSK Investigational Site
Leipzig, Saxony, 04103
GSK Investigational Site
Mainz, Rhineland-Palatinate, 55131
GSK Investigational Site
Münster, North Rhine-Westphalia, 48149
France5 sites
GSK Investigational Site
Bobigny, 93009
GSK Investigational Site
Lille, 59037
GSK Investigational Site
Marseille, 13273
GSK Investigational Site
Pierre-Bénite, 69495
GSK Investigational Site
Toulouse, 31059
Belgium2 sites
GSK Investigational Site
Ghent, 9000
GSK Investigational Site
Leuven, 3000
About this study
Official title: An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias
MEK111759 is a dose-escalation, Phase I/II, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 in subjects with relapsed or refractory leukemias. The recommended dose and regimen will be selected based on the safety, pharmacokinetic, and pharmacodynamic profiles. This study will identify the maximum tolerated and recommended Phase II doses using a dose-escalation procedure. Dose escalations will continue based on predefined parameters until a maximum tolerated dose is established. In Phase II, the clinical efficacy of GSK1120212 in subjects with relapsed or refractory leukaemias (AML, MDS or CMML) will be determined.
- Conditions
- Cancer
- Being tested
- GSK1120212
- Keywords
- Oncology, GSK1120212, MEK inhibitor, hematological malignancies, AML, CMML, MDS
- Medical subject headings
- Neoplasms, Hematologic Neoplasms, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1120212Drug
Starting dose based on GSK protocol MEK111054 and then dose escalation based on Dose Limiting Toxicities per protocol.
GSK1120212Drug
Dose will be maximum tolerated dose based on Phase I results.
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | The proposed treatment schedule of GSK1120212 is continuous daily dosing. At the initiation of dosing, a loading dose will be given prior to starting continuous dosing (maintenance dose).
Alterations to the dose and schedule will be based on emerging PK, PD, and tolerability data. The goal will be to define a regimen that is well tolerated and provides adequate PK and PD. This will be the recommended Phase II schedule. Receives: Drug: GSK1120212 |
| Phase II | Experimental | A dose determined by Phase I to further evaulate the safety profile, PK, PD, and clinical activity of GSK1120212. Receives: Drug: GSK1120212 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) by Dose
An AE is any untoward medical occurrence in a participant (par.) or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Hematology Parameters by Dose
Hematology and clinical chemistry data were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Hematology tests where the toxicity grade is defined by NCI-CTCAE includes hemoglobin, international normalized ratio (INR), lymphocytes, total neutrophils, platelet count, and partial thromboplastin time (PTT). Participants with missing baseline grades were assumed to have a baseline grade of 0. Only those participants (par.) with laboratory values for worst-case on-therapy (defined as the worst shift that occurred at any time during the treatment period) are presented.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Chemistry Parameters by Dose
Hematology and clinical chemistry data were summarized according to NCI-CTCAE grade, version 3.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Clinical chemistry tests where the toxicity grade is defined by NCI-CTCAE includes albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase (AST), total bilirubin, calcium, creatinine, glucose, bicarbonate, potassium, magnesium, sodium, and phosphorus. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Only those participants (par.) with laboratory values for worst-case on-therapy are presented.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Number of Participants With a Change From Baseline in Heart Rate by Dose
Change from Baseline in heart rate is categorized as decrease to <60 beats per minute (bpm), change to normal or no change, and increase to >100 bpm. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants are counted twice if the participant heart rate value decreased to <60 bpm and increased to >100 bpm post-baseline. Only those participants (par.) with heart rate values for worst-case on-therapy are presented.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Number of Participants With a Change From Baseline in Systolic and Diastolic Blood Pressure by Dose
Change from Baseline in systolic blood pressure (SBP) is categorized as: Grade 0 (<120 millimeters of mercury [mmHg]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), and Grade 3/4 (>=160 mmHg). Change from Baseline in diastolic blood pressure (DBP) is categorized as: Grade 0 (<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), and Grade 3/4 (>=100 mmHg). An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values are assumed to have a Baseline value of grade 0. Only those participants (par.) with blood pressure values for worst-case on-therapy are presented.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Number of Participants With a Change From Baseline in Temperature by Dose
Change from Baseline in temperature is categorized as a decrease to <=35 degrees celsius (C), change to normal or no change, and increase to >=38 degrees C. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants (par.) are counted twice if the participant temperature value decreased to <=35 degrees C and increased to >=38 degrees C post-Baseline. Only those participants with temperature values for worst-case on-therapy are presented.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Number of Participants With an Investigator-assessed Best Response (Achieving Complete Response [CR], Marrow CR, Partial Response [PR], Complete Response Without Platelet Recovery [CRp] or Morphologic Leukaemia-free State[MLFS]) by Cohort
Overall response rate (ORR=CR+CRp+Marrow CR+MLFS+PR) was calculated from the investigator's assessment of response recorded within the first eight weeks of treatment. CR includes complete remission. Complete remission is a state in which the participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >=1 x 10^9/L, platelet count >=100 x 10^9/L, and normal marrow differential (<=5% blasts). PR includes partial remission. Partial remission is a state in which the participant has a CR with 6 to 25% abnormal cells in the marrow or 50% decrease in bone marrow blasts. CRp is as per CR but platelet count <100 x 10^9/L. MLFS is a state in which the participant has a normal marrow differential (<5% blasts), neutrophil, and platelet counts are not considered.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days)
Secondary outcomes (7)
AUC(0-24), AUC(0-t), and AUC(0-tau) of GSK1120212 in Part 1
Area under the concentration-time (AUC) curve from time zero (pre-dose) to 24 hours (AUC[0-24]) for Cycle 1 Day 1 (C1D1), from time zero to the last time of a quantifiable concentration (AUC[0-t]) for C1D1 and Cylce 1 Day 15 (C1D15) and AUC curve over the dosing interval AUC[0-tau] for C1D15 were measured. Blood samples for PK analysis were taken on Day 1 and Day 15 (within 30 minutes [min] before study drug administration) and at 0.5 hour (h), 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 24 h post-dose. All other PK sampling were done pre-dose (i.e., within 30 min before study drug administration).
Measured: Cycle 1 Day 1 and Cycle 1 Day 15
Cmin and Cmax of GSK1120212 in Part 1
Cmax is defined as the maximum observed concentration of GSK1120212 and was measured for C1D1 and C1D15. Cmin is defined as the minimal observed concentration of GSK1120212 and was measured for C1D15. Blood samples for PK analysis were taken on Day 1 and Day 15 (within 30 min before study drug administration) and at 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 24 h post-dose. All other PK sampling were done pre-dose (i.e., within 30 min before study drug administration).
Measured: Cycle 1 Day 1 and Cycle 1 Day 15
t1/2 at C1D1 and t1/2 Effective (Eff.) at C1D15 of GSK1120212 in Part 1
t1/2 is defined as terminal phase half-life, which is the time required for the amount of the drug in the body to decrease by half and was measured for C1D1. t1/2eff. is defined as the effective half-life and was measured for C1D15. Blood samples for PK analysis were taken on Day 1 and Day 15 (within 30 min before study drug administration) and at 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 24 h post-dose. All other PK sampling were done pre-dose (i.e., within 30 min before study drug administration).
Measured: Cycle 1 Day 1 (t1/2) and Cycle 1 Day 15 (t1/2eff)
Tmax of GSK1120212 in Part 1
Tmax is defined as the time to reach the observed maximum concentration and was measured for C1D1 and C1D15. Blood samples for PK analysis were taken on Day 1 and Day 15 (within 30 min before study drug administration) and at 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 24 h post-dose. All other PK sampling were done pre-dose (i.e., within 30 min before study drug administration).
Measured: Cycle 1 Day 1 and Cycle 1 Day 15
Accumulation Ratio (AR) of GSK1120212 in Part 1
AR is the ratio of the Day 15 AUC0-tau (0 hour to last dose interval) and Day 1 AUC0-tau (AUCtau C1D15/AUCtau C1D1). Blood samples for PK analysis were taken on Day 1 and Day 15 (within 30 min before study drug administration) and at 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 24 h post-dose. All other PK sampling were done pre-dose (i.e., within 30 min before study drug administration).
Measured: Cycle 1 Day 1 and Cycle 1 Day 15
Ctau of GSK1120212 in Part 2
Ctau is the pre-dose (trough) concentration at the end of the dosing interval and was measured for Cycle 1 Day 15 (C1D15), Cycle 2 Day 1(C2D1), Cylce 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), Cycle 7 Day 1 (C7D1), Cycle 8 Day 1 (C8D1), Cycle 9 Day 1 (C9D1), Cycle 10 Day 1 (C10D1), Cycle 11 Day 1 (C11D1) and Cycle 12 Day 1 (C12D1). Blood samples for PK analysis were collected pre-dose (i.e., no later than 15 min prior to dosing).
Measured: C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1 and C12D1
Overall Survival by Cohort
Overall survival is defined as the time from the start of study treatment (GSK1120212) until death due to any cause. For the analysis of overall survival, the last date of known contact was used for those participants who had not died at the time of analysis; such participants were considered censored.
Measured: From the start of the study drug until the final study visit (up to approximately 407 days )
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2009 (estimated)
- Study startMay 2011
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00920140
- Sponsor's protocol ID
- 111759
- Status last verified
- Mar 2014
- First submitted
- 12 Jun 2009
- Last updated
- 2 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias
- ClinicalTrials.gov ID
- NCT00920140
- Acronym / sponsor ID
- 111759
- Conditions
- Cancer
- Keywords
- Oncology, GSK1120212, MEK inhibitor, hematological malignancies, AML, CMML, MDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- May 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 15 Jun 2009 (estimated)
- Results
- Posted 28 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MEK111759 is a dose-escalation, Phase I/II, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 in subjects with relapsed or refractory leukemias. The recommended dose and regimen will be selected based on the safety, pharmacokinetic, and pharmacodynamic profiles. This study will identify the maximum tolerated and recommended Phase II doses using a dose-escalation procedure. Dose escalations will continue based on predefined parameters until a maximum tolerated dose is established. In Phase II, the clinical efficacy of GSK1120212 in subjects with relapsed or refractory leukaemias (AML, MDS or CMML) will be determined.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: GSK1120212The proposed treatment schedule of GSK1120212 is continuous daily dosing. At the initiation of dosing, a loading dose will be given prior to starting continuous dosing (maintenance dose). Alterations to the dose and schedule will be based on emerging PK, PD, and tolerability data. The goal will be to define a regimen that is well tolerated and provides adequate PK and PD. This will be the recommended Phase II schedule. |
| Phase II | Experimental | Drug: GSK1120212A dose determined by Phase I to further evaulate the safety profile, PK, PD, and clinical activity of GSK1120212. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Phase I
- Written informed consent provided.
- 18 years old or older.
- Subjects must have relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Subjects with poor-risk myelodysplasia (MDS) and chronic melomonocytic leukemia (CMML) are also eligible. Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blast crisis. Subjects with agnogenic myeloid metaplasia (AMM) are also eligible. Subjects with a haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant are NOT eligible.
- Subjects who have previously received an autologous stem cell transplant are allowed if a minimum of three months has elapsed from the time of transplant (T0) and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK1120212.
Key exclusion criteria (25 listed)
- Phase I
- Currently receiving cancer therapy as specified in the protocol.
- Received corticosteroids or imatinib within 24h of GSK1120212 administration.
- Received gemtuzumab ozogamicin (myelotarg) within two weeks of GSK1120212 adminstration.
- Received an investigational anti-cancer drug within four weeks or five half-lives, whichever is shorter of GSK1120212 administration, as specified in the protocol.
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 |
|---|---|---|
| GSK1120212Starting dose based on GSK protocol MEK111054 and then dose escalation based on Dose Limiting Toxicities per protocol. | Drug | Phase I |
| GSK1120212Dose will be maximum tolerated dose based on Phase I results. | Drug | Phase II |
Primary outcome
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) by Dose
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
An AE is any untoward medical occurrence in a participant (par.) or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Hematology Parameters by Dose
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
Hematology and clinical chemistry data were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Hematology tests where the toxicity grade is defined by NCI-CTCAE includes hemoglobin, international normalized ratio (INR), lymphocytes, total neutrophils, platelet count, and partial thromboplastin time (PTT). Participants with missing baseline grades were assumed to have a baseline grade of 0. Only those participants (par.) with laboratory values for worst-case on-therapy (defined as the worst shift that occurred at any time during the treatment period) are presented.
Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Chemistry Parameters by Dose
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
Hematology and clinical chemistry data were summarized according to NCI-CTCAE grade, version 3.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe; Grade 4, Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Clinical chemistry tests where the toxicity grade is defined by NCI-CTCAE includes albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase (AST), total bilirubin, calcium, creatinine, glucose, bicarbonate, potassium, magnesium, sodium, and phosphorus. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Only those participants (par.) with laboratory values for worst-case on-therapy are presented.
Number of Participants With a Change From Baseline in Heart Rate by Dose
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
Change from Baseline in heart rate is categorized as decrease to <60 beats per minute (bpm), change to normal or no change, and increase to >100 bpm. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants are counted twice if the participant heart rate value decreased to <60 bpm and increased to >100 bpm post-baseline. Only those participants (par.) with heart rate values for worst-case on-therapy are presented.
Number of Participants With a Change From Baseline in Systolic and Diastolic Blood Pressure by Dose
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
Change from Baseline in systolic blood pressure (SBP) is categorized as: Grade 0 (<120 millimeters of mercury [mmHg]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), and Grade 3/4 (>=160 mmHg). Change from Baseline in diastolic blood pressure (DBP) is categorized as: Grade 0 (<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), and Grade 3/4 (>=100 mmHg). An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values are assumed to have a Baseline value of grade 0. Only those participants (par.) with blood pressure values for worst-case on-therapy are presented.
Number of Participants With a Change From Baseline in Temperature by Dose
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
Change from Baseline in temperature is categorized as a decrease to <=35 degrees celsius (C), change to normal or no change, and increase to >=38 degrees C. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants (par.) are counted twice if the participant temperature value decreased to <=35 degrees C and increased to >=38 degrees C post-Baseline. Only those participants with temperature values for worst-case on-therapy are presented.
Number of Participants With an Investigator-assessed Best Response (Achieving Complete Response [CR], Marrow CR, Partial Response [PR], Complete Response Without Platelet Recovery [CRp] or Morphologic Leukaemia-free State[MLFS]) by Cohort
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days)
Overall response rate (ORR=CR+CRp+Marrow CR+MLFS+PR) was calculated from the investigator's assessment of response recorded within the first eight weeks of treatment. CR includes complete remission. Complete remission is a state in which the participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >=1 x 10^9/L, platelet count >=100 x 10^9/L, and normal marrow differential (<=5% blasts). PR includes partial remission. Partial remission is a state in which the participant has a CR with 6 to 25% abnormal cells in the marrow or 50% decrease in bone marrow blasts. CRp is as per CR but platelet count <100 x 10^9/L. MLFS is a state in which the participant has a normal marrow differential (<5% blasts), neutrophil, and platelet counts are not considered.
7 secondary outcomes
AUC(0-24), AUC(0-t), and AUC(0-tau) of GSK1120212 in Part 1
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15
Cmin and Cmax of GSK1120212 in Part 1
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15
t1/2 at C1D1 and t1/2 Effective (Eff.) at C1D15 of GSK1120212 in Part 1
Time frame: Cycle 1 Day 1 (t1/2) and Cycle 1 Day 15 (t1/2eff)
Tmax of GSK1120212 in Part 1
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15
Accumulation Ratio (AR) of GSK1120212 in Part 1
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15
Ctau of GSK1120212 in Part 2
Time frame: C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1 and C12D1
Overall Survival by Cohort
Time frame: From the start of the study drug until the final study visit (up to approximately 407 days )
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
28 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK1120212 in people with Cancer, run by GlaxoSmithKline at 28 sites in 4 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 16 inclusion and 25 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 2 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Germany, France, Belgium. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 28 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) by Dose (time frame: From the start of the study drug until the final study visit (up to approximately 407 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2014; AzTrials last refreshed its copy on 30 Oct 2026.