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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Phase II | Experimental | A dose determined by Phase I to further evaulate the safety profile, PK, PD, and clinical activity of GSK1120212. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1120212 | Drug | Starting dose based on GSK protocol MEK111054 and then dose escalation based on Dose Limiting Toxicities per protocol. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Cohorts 1: RAS Positive AML/MDS Cohort 2: Wild Type AML/MDS/CMML Cohort 3: RAS Positive CMML
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Birmingham | Alabama | 35249 | United States | ||
| GSK Investigational Site |
This is a Phase I/II study. Phase I is a dose escalation phase in participants with relapsed or refractory leukaemias to identify the recommended dose of GSK1120212 for Phase II. Phase II further evaluates the safety and efficacy of the recommended dose.
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| ID | Title | Description |
|---|---|---|
| FG000 | GSK1120212 < 2 mg OD | Participants with relapsed or refractory leukemias received either GSK1120212 3 milligrams (mg) loading dose (LD) followed by 1 mg once daily (OD) (3/1 mg LD/OD), or 1 mg OD as a continuous dose. |
| FG001 | GSK1120212 2 mg OD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1 (Dose Escalation) |
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| GSK1120212 | Drug | Dose will be maximum tolerated dose based on Phase I results. |
|
| 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. | 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. | 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. | 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. | From the start of the study drug until the final study visit (up to approximately 407 days) |
| 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). | 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). | 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). | 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). | 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). | 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. | From the start of the study drug until the final study visit (up to approximately 407 days ) |
| Duarte |
| California |
| 91010 |
| United States |
| GSK Investigational Site | Los Angeles | California | 90095 | United States |
| GSK Investigational Site | San Francisco | California | 94143 | United States |
| GSK Investigational Site | Chicago | Illinois | 60611 | United States |
| GSK Investigational Site | Rochester | Minnesota | 55905 | United States |
| GSK Investigational Site | Bornx | New York | 10467 | United States |
| GSK Investigational Site | Lake Success | New York | 11042 | United States |
| GSK Investigational Site | New York | New York | 10032 | United States |
| GSK Investigational Site | Winston-Salem | North Carolina | 27157-1009 | United States |
| GSK Investigational Site | Portland | Oregon | 97239 | United States |
| GSK Investigational Site | Hershey | Pennsylvania | 17033 | United States |
| GSK Investigational Site | Pittsburgh | Pennsylvania | 15232 | United States |
| GSK Investigational Site | Houston | Texas | 77030 | United States |
| GSK Investigational Site | Seattle | Washington | 98109-1023 | United States |
| GSK Investigational Site | Ghent | 9000 | Belgium |
| GSK Investigational Site | Leuven | 3000 | Belgium |
| GSK Investigational Site | Bobigny | 93009 | France |
| GSK Investigational Site | Lille | 59037 | France |
| GSK Investigational Site | Marseille | 13273 | France |
| GSK Investigational Site | Pierre-Bénite | 69495 | France |
| GSK Investigational Site | Toulouse | 31059 | France |
| GSK Investigational Site | Frankfurt am Main | Hesse | 60590 | Germany |
| GSK Investigational Site | Duisburg | North Rhine-Westphalia | 47166 | Germany |
| GSK Investigational Site | Münster | North Rhine-Westphalia | 48149 | Germany |
| GSK Investigational Site | Mainz | Rhineland-Palatinate | 55131 | Germany |
| GSK Investigational Site | Dresden | Saxony | 01307 | Germany |
| GSK Investigational Site | Leipzig | Saxony | 04103 | Germany |
Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose. |
| FG002 | Cohort 1: AML/MDS With RAS Mutation | Participants with relapsed or refractory acute myeloid leukemia (AML) or myelodysplasia (MDS) with rat sarcoma (RAS) mutation received GSK1120212 2 mg OD as a continuous dose. |
| FG003 | Cohort 2: AML/MDS/CMML With RAS wt/Unknown | Participants with relapsed or refractory AML or MDS or chronic myelomonocytic leukemia (CMML) with RAS wild type (wt) or unknown mutation received GSK1120212 2 mg OD as a continuous dose. |
| FG004 | Cohort 3: CMML With RAS Mutation | Participants with relapsed or refractory CMML with RAS mutation received GSK1120212 2 mg OD as a continuous dose. |
| COMPLETED |
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| NOT COMPLETED |
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| Phase 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | GSK1120212 <2 mg OD | Participants with relapsed or refractory leukemias received either GSK1120212 3 milligrams (mg) loading dose (LD) followed by 1 mg once daily (OD) (3/1 mg LD/OD), or 1 mg OD as a continuous dose. |
| BG001 | GSK1120212 2 mg OD | Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose. |
| BG002 | Cohort 1: AML/MDS With RAS Mutation | Participants with relapsed or refractory AML or MDS with RAS mutation received GSK1120212 2 mg OD as a continuous dose. |
| BG003 | Cohort 2: AML/MDS/CMML With RAS wt/Unknown | Participants with relapsed or refractory AML or MDS or CMML with RAS wt or unknown mutation received GSK1120212 2 mg OD as a continuous dose. |
| BG004 | Cohort 3: CMML With RAS Mutation | Participants with relapsed or refractory CMML with RAS mutation received GSK1120212 2 mg OD as a continuous dose. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
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| Primary | 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. | All Treated Population: all participants who received at least one dose of study medication. Safety data was evaluated based on this population. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Primary | 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. | All Treated Population (ATP). Only those par. available at the specified time points were analyzed. Different par. may have been analyzed for different parameters; the overall number analyzed reflects everyone in the ATP. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Primary | 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. | All Treated Population (ATP). Only those par. available at the specified time points were analyzed. Different par. may have been analyzed for different parameters; the overall number analyzed reflects everyone in the ATP. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Primary | 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. | All Treated Population (ATP). Only those par. available at the specified time points were analyzed. Different par. may have been analyzed for different parameters; the overall number analyzed reflects everyone in the ATP. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Primary | 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. | All Treated Population (ATP). Only those par. available at the specified time points were analyzed. Different par. may have been analyzed for different parameters; the overall number analyzed reflects everyone in the ATP. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Primary | 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. | All Treated Population (ATP). Only those par. available at the specified time points were analyzed. Different par. may have been analyzed for different parameters; the overall number analyzed reflects everyone in the ATP. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Primary | 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. | Efficacy Population: all participants included in the All Treated Population who had received at least one dose of 2 mg of study drug in Phase 2. The number of participants for the Cohort 2: AML/MDS/CMML with RAS wt/Unknown treatment group is equal to the 8 participants from Phase 1 plus the 22 participants from Phase 2 (total of 30). | Posted | Number | Participants | From the start of the study drug until the final study visit (up to approximately 407 days) |
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| Secondary | 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). | Pharmacokinetic Population: all participants included in the All Treated Population for whom a PK sample was obtained and analyzed. Only participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hour/milliliter | Cycle 1 Day 1 and Cycle 1 Day 15 |
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| Secondary | 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). | Pharmacokinetic Population. Only participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Cycle 1 Day 1 and Cycle 1 Day 15 |
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| Secondary | 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). | Pharmacokinetic Population. Only participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Cycle 1 Day 1 (t1/2) and Cycle 1 Day 15 (t1/2eff) |
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| Secondary | 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). | Pharmacokinetic Population. Only participants with data available at the indicated time points were analyzed. | Posted | Median | Full Range | Hours | Cycle 1 Day 1 and Cycle 1 Day 15 |
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| Secondary | 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). | Pharmacokinetic Population. Only participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Cycle 1 Day 1 and Cycle 1 Day 15 |
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| Secondary | 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). | Pharmacokinetic Population. Only participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1 and C12D1 |
|
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| Secondary | 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. | Efficacy Population. The number of participants for the Cohort 2: AML/MDS/CMML with RAS wt/Unknown treatment group is equal to the 8 participants from Phase 1 plus the 22 participants from Phase 2 (total of 30). | Posted | Median | 90% Confidence Interval | Months | From the start of the study drug until the final study visit (up to approximately 407 days ) |
|
Serious adverse events (SAEs) and non-serious AEs were collected from the start of study drug until the final study visit (up to approximately 407 days).
SAEs and non-serious AEs were collected in members of the All treated Population, comprised of all participants (par.) who received at least one dose of study medication. One Phase 2 par. was incorrectly dosed (received <2 mg [0.5 mg]); thus, 6 par. receiving GSK1120212 <2 mg OD were analyzed. .
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GSK1120212 <2 mg OD | Participants with relapsed or refractory leukemias received either GSK1120212 3 mg LD followed by 1 mg OD (3/1 mg LD/OD), or 1 mg OD as a continuous dose. | 2 | 6 | 6 | 6 | ||
| EG001 | GSK1120212 2 mg OD | Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose. | 64 | 91 | 90 | 91 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Oral infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Enterococcal bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Epiglottitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Streptococcal bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Zygomycosis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Atrioventricular block | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Left ventricular failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Mitral valve incompetence | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Ileus paralytic | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Extrapyramidal disorder | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Acute febrile neutrophilic dermatosis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Ischaemia | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Graft versus host disease in intestine | Immune system disorders | MedDRA | Systematic Assessment |
| |
| Blood culture positive | Investigations | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Neck mass | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Rectal ulcer | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Systematic Assessment |
| |
| Chills | General disorders | MedDRA | Systematic Assessment |
| |
| Pain | General disorders | MedDRA | Systematic Assessment |
| |
| Swelling | General disorders | MedDRA | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypouricaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Enterococcal infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Herpes simplex | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Vulval cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Brain natriuretic peptide increased | Investigations | MedDRA | Systematic Assessment |
| |
| Prothrombin time prolonged | Investigations | MedDRA | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood potassium increased | Investigations | MedDRA | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA | Systematic Assessment |
| |
| Glaucoma | Eye disorders | MedDRA | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D019337 | Hematologic Neoplasms |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| C560077 | trametinib |
Not provided
Not provided
Not provided
| Lack of Efficacy |
|
| Lost to Follow-up |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| Male |
|
| White - White/Caucasian/European Heritage |
|
| Asian - Central/South Asian Heritage |
|
| Asian - Japanese Heritage |
|
| Asian - South East Asian Heritage |
|
| Missing |
|
| OG001 | GSK1120212 2 mg OD | Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose. |
|
|
| GSK1120212 2 mg OD |
Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG001 | Cohort 2: AML/MDS/CMML With RAS wt/Unknown | Participants with relapsed or refractory AML or MDS or CMML with RAS wt or unknown mutation received GSK1120212 2 mg OD as a continuous dose. |
| OG002 | Cohort 3: CMML With RAS Mutation | Participants with relapsed or refractory CMML with RAS mutation received GSK1120212 2 mg OD as a continuous dose. |
|
|
| GSK1120212 2 mg OD |
Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose. |
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
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