Safety, Clinical Activity, Pharmacokinetics (PK) and Pharmacodynamics Study of GSK2879552, Alone or With Azacitidine, in Subjects With High Risk Myelodysplastic Syndromes (MDS)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02929498
• Collaborator: Parexel (Industry)
• Enrollment: 7
• Locations: 6
• Arms: 2
• Actual Duration (Months): 6
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase I/II, open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in subjects with MDS. The study consisted of 2 parts. The objective of Part 1 is to determine the recommended phase 2 dose (RP2D) of GSK2879552 administered alone and in combination with azacitidine in adult subjects with high risk MDS previously treated with HMA. The objective of Part 2 is to evaluate clinical activity after treatment with GSK2879552, alone or in combination with azacitidine, in adult subjects with high risk MDS previously treated with HMA.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome; Myelodysplastic Syndromes	Drug: GSK2879552; Drug: Azacitidine	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-label, 2 Arm Study to Investigate the Safety, Clinical Activity, Pharmacokinetics and Pharmacodynamics of GSK2879552 Administered Alone or in Combination With Azacitidine, in Adult Subjects With IPSS-R High and Very High Risk Myelodysplastic Syndromes (MDS) Previously Treated With Hypomethylating Agents (HMA)
• Actual Study Start Date: Jul 31, 2017
• Actual Primary Completion Date: Jan 31, 2018
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: GSK2879552 monotherapy Subjects will receive GSK2879552 2 milligrams (mg) once daily in each 28 day cycle.	Drug: GSK2879552; GSK2879552 will be administered orally as continuous daily dosing.
Experimental: Arm B: GSK2879552+Azacitidine combination therapy Subjects will receive GSK2879552 starting at 1 mg once daily in each 28 day cycle and Azacitidine 75 mg/square meter (m2) from Day 1 to Day 7 of each 28 day cycle.	Drug: GSK2879552; GSK2879552 will be administered orally as continuous daily dosing.; Drug: Azacitidine; Azacitidine will be administered at 75 mg/m2 from Day 1 to Day 7 of each 28 day cycle by intravenous (iv) infusion or subcutaneous (sc) injection.

Outcome Measures

Primary Outcome Measures

1. Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities [Up to 2 years]

   An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. An event was considered a DLT if it occurred within the first 28 days of treatment, and met the DLT criteria unless it could be clearly established that the event was unrelated to treatment.

2. Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

3. Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

4. Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

5. Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

6. Part 1: Change From Baseline in Hematocrit at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

7. Part 1: Change From Baseline in Erythrocytes at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

8. Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1) (each cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

9. Part 1: Change From Baseline in Blast/Leukocytes at Indicated Time-points [Baseline and Day 1 of Cycle 1 (Cycle of 28 days)]

   Blood samples were collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

10. Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Blood samples were collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

11. Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Blood samples were collected from participants for evaluation of clinical chemistry parameters including calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

12. Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Blood samples were collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

13. Part 1: Change From Baseline in Partial Pressure Carbon Dioxide (pCO2) at Indicated Time Points [Baseline and Day 1 of Cycle 1 (cycle of 28 days)]

    Blood samples were collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

14. Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points [Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Vital signs including SBP and DBP were measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

15. Part 1: Change From Baseline in Heart Rate at Indicated Time-points [Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Vital signs including heart rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

16. Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points [Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Vital signs including respiratory rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

17. Part 1: Change From Baseline in Body Temperature at Indicated Time-points [Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Vital signs including body temperature was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

18. Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points [Baseline and Cycle 1 (Days 1, 7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

19. Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points [Baseline and Cycle 1 (Days 1,7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

20. Part 1: Number of Participants With Abnormal Findings During Physical Examination [Up to 2 years]

    A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

21. Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR) [Up to 2.5 years]

    CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. International Working Group (IWG) criteria, 2006 was to be used to evaluate response.

22. Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR) [Up to 2.5 years]

    Objective response rate was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. IWG criteria, 2006 was to be used to evaluate response.

23. Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points [Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)]

    Blood samples were collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.

Secondary Outcome Measures

1. Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR) [Up to 2 years]

   Clinical Benefit Rate was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.

2. Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR) [Up to 2 years]

   Objective Response Rate was defined as the percentage of participants who achieved Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.

3. Part 1: Plasma Concentration of GSK2879552 [Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)]

   Blood samples were collected at indicated time points to evaluate concentration of GSK2879552. Each Pharmacokinetic (PK) sample was collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. PK Concentration Population consisted of all participants in the All Treated Subject Population for whom a blood sample for pharmacokinetics was obtained and analyzed.

4. Part 1: Plasma Concentration of Azacitidine [Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)]

   Blood samples were to be collected at indicated time points to evaluate concentration of Azacitidine.

5. Part 1: Duration of Response [Up to 2 years]

   Duration of response is defined as the subset of participants (responders) who show a response (CR, mCR, PR, or HI), the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the DOR was to be censored at last disease assessment.

6. Part 1: Progression-free Survival [Up to 2 years]

   Progression-free survival (PFS) is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was censored at the date of the last adequate assessment.

7. Part 1: Overall Survival [Up to 2 years]

   Overall survival (OS) is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival (OS), 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.

8. Part 1: Proportion of Participants With Disease Progression to Acute Myeloblastic Leukemia (AML) [Up to 2 years]

   The proportion of participants with disease progression to AML is defined as the percentage of participants experiencing AML on the All Treated Subjects Population.

9. Part 1: Time to AML Progression [Up to 2 years]

   Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.

10. Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month [Up to 2 years]

    Number of participants with documented platelet and RBC transfusions have been presented.

11. Part 2: Number of Participants With Any AEs and SAEs [Up to 2.5 years]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE.

12. Part 2: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

13. Part 2: Change From Baseline in MCV at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

14. Part 2: Change From Baseline in MCH at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

15. Part 2: Change From Baseline in MCHC and Hb at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

16. Part 2: Change From Baseline in Hematocrit at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

17. Part 2: Change From Baseline in Erythrocytes at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

18. Part 2: Change From Baseline in Percent Reticulocytes at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

19. Part 2: Change From Baseline in Blast/Leukocytes at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

20. Part 2: Change From Baseline in ALT, ALP, AST, LDH and GGT at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

21. Part 2: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

22. Part 2: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

23. Part 2: Change From Baseline in Albumin and Protein at Indicated Time Points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

24. Part 2: Change From Baseline in pCO2 at Indicated Time Points [Baseline and up to 2.5 years]

    Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

25. Part 2: Change From Baseline in SBP and DBP at Indicated Time-points [Baseline and up to 2.5 years]

    Vital signs including SBP and DBP were to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

26. Part 2: Change From Baseline in Heart Rate at Indicated Time-points [Baseline and up to 2.5 years]

    Vital signs including heart rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

27. Part 2: Change From Baseline in Respiratory Rate at Indicated Time-points [Baseline and up to 2.5 years]

    Vital signs including respiratory rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

28. Part 2: Change From Baseline in Body Temperature at Indicated Time-points [Baseline and up to 2.5 years]

    Vital signs including body temperature was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

29. Part 2: Change From Baseline in ECG Mean Heart Rate at Indicated Time-points [Baseline and up to 2.5 years]

    Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

30. Part 2: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time-points [Baseline and up to 2.5 years]

    Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.

31. Part 2: Number of Participants With Abnormal Findings During Physical Examination [Up to 2.5 years]

    A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).

32. Part 2: Plasma Clearance (CL/F) of GSK2879552 [Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Day 4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3 to 1 (each cycle of 28 days)]

    Blood samples were to be collected at indicated time points to evaluate CL/F of GSK2879552. Each PK sample was to be collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days.

33. Part 2: Duration of Response [Up to 2.5 years]

    Duration of response is defined as the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the duration of response was to be censored at last disease assessment.

34. Part 2: Progression-free Survival [Up to 2.5 years]

    Progression-free survival is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was to be censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was to be censored at the date of the last adequate assessment.

35. Part 2: Overall Survival [Up to 2.5 years]

    Overall survival is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival, the last date of known contact was to be used for those participants who had not died at the time of analysis; such participants were to be considered censored.

36. Part 2: Percentage of Participants With Disease Progression to AML [Up to 2.5 years]

    The percentage of participants experiencing AML on the All Treated Subjects Population was to be presented.

37. Part 2: Time to AML Progression [Up to 2.5 years]

    Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was to be censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.

38. Part 2: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month [Up to 2.5 years]

    Number of participants with documented platelet and RBC transfusions were to be presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• =18 years of age and provided signed written informed consent

• Subjects must have IPSS-R high or very high risk myelodysplastic syndromes (MDS) by World Health Organization (WHO) classification

• Subjects must have failed hypomethylating treatment where "failure" is defined as: Progression (according to 2006 International Working Group [IWG] criteria) at any time after initiation of the hypomethylating treatment OR Failure to achieve complete or partial response or hematological improvement (HI) (according to 2006 IWG) after at least 4 cycles treatment OR Relapse after initial complete or partial response or HI (according to 2006 IWG criteria).

• Subjects are not a candidate, or have failed allogeneic stem cell transplantation. Subjects who underwent allo-transplant in the past are eligible under following conditions: transplant was >2 year prior to enrolment, and no evidence of active graft-versus-host disease (GVHD)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Subjects must have a life expectancy of at least 12 weeks, in the opinion of the investigator.

• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

• All prior treatment-related toxicities must be National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 at the time of enrollment (except for alopecia).

• Adequate baseline organ function defined by: International Normalization Ratio (INR) and activated partial thromboplastin time (aPTT) <=1.3xupper limit of normal (ULN); platelet count (PLT) >=10,000 (transfusions permitted to bring PLT to >10,000); total bilirubin <=1.5xULN (Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35% or subject has a diagnosis of Gilbert's syndrome); Alanine transaminase (ALT) <=2.5xULN; creatinine <=1.5xULN OR calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or measured from 24 hour urine >=50 milliliters (mL)/minute (min); and Ejection fraction >=lower limit of normal (LLN) by Echocardiogram (ECHO) or multigated acquisition scan (MUGA)

• Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 7 days following the last dose of study treatment.

• Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the administration of the first dose of study treatment until 3 months after the last dose of study treatment to allow for clearance of any altered sperm.

Exclusion Criteria:

• AML according to world health organization (WHO) criteria (i.e. bone marrow blasts

20%)

• Active hepatitis B or hepatitis C treatment

• Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower

• History of or concurrent malignancy of solid tumours, except for below:

Exception: Subjects who have been disease-free for 2 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

• Prior treatment with temozolomide, dacarbazine or procarbazine

• Prior treatment with poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (example (e.g.), olaparib, veliparib [ABT-888])

• Currently receiving other anti-cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery, and/or tumour embolization)

• Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration

• Evidence of severe or uncontrolled systemic diseases (e.g., severe/chronic infection, unstable or uncompensated respiratory, renal, or cardiac disease). Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator

• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator's assessment)

• Patients with any major bleeding current or within the past 4 weeks. (e.g. recent gastrointestinal [GI] hemorrhage or neurosurgery).

• Administration of an investigational drug within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study treatment(s) in this study.

• Cardiac abnormalities as evidenced by any of the following: clinically significant uncontrolled arrhythmias or uncontrolled hypertension; history or evidence of current

=Class II congestive heart failure as defined by New York Heart Association (NYHA); history of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months; baseline Corrected QT (QTc) interval using Fridericia's formula >450 milliseconds (msec) or 480 msec in subjects with Bundle Branch Block. QTc value based on single or average of triplicate ECGs obtained over a brief recording period

• Current use of a prohibited medication including anticoagulants or platelet inhibitors or expected to require any of these medications during treatment with the investigational drug

• Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug

• Lactating female

• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or lysine-specific demethylase 1 (LSD1) inhibitors that contraindicates their participation

• Known hypersensitivity to azacitidine or mannitol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Augusta	Georgia	United States	30912
2	GSK Investigational Site	Durham	North Carolina	United States	27705
3	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19111
4	GSK Investigational Site	Houston	Texas	United States	77030
5	GSK Investigational Site	Madrid		Spain	28033
6	GSK Investigational Site	Valencia		Spain	46026

Sponsors and Collaborators

• GlaxoSmithKline
• Parexel

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - May 8, 2017
• Statistical Analysis Plan - Jun 21, 2018

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02929498
• Other Study ID Numbers: 205744; 2016-002294-35
• First Posted: Oct 11, 2016
• Last Update Posted: May 14, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: GSK2879552; Revised International Prognostic Scoring System (IPSS-R); azacitidine; hypomethylating agents; myelodysplastic syndrome
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Azacitidine

Study Results

Participant Flow

Recruitment Details	This was an open-label, 2 arm study to evaluate the safety and clinical activity of GSK2879552 alone, or in combination with azacitidine in adult participants with myelodysplastic syndromes (MDS). The study was conducted in 3 centers among 2 countries.
Pre-assignment Detail	Total 5 participants were included into Part 1 and received GSK2879552. The study was terminated during Part 1 and hence Part 2 was not conducted as the risk benefit in earlier studies do not favor continuation of this study.

Arm/Group Title	Part 1: GSK2879552	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Period Title: Part 1: Dose Confirmation (Upto 2 Years)
STARTED	5	0	0
COMPLETED	0	0	0
NOT COMPLETED	5	0	0
Period Title: Part 1: Dose Confirmation (Upto 2 Years)
STARTED	0	0	0
COMPLETED	0	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1: GSK2879552	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine	Total
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).	Total of all reporting groups
Overall Participants	5	0	0	5
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	77.2 (5.07)	77.2 (5.07)
Sex: Female, Male (Count of Participants)
Female	3 60%	0 NaN	0 NaN	3 60%
Male	2 40%	0 NaN	0 NaN	2 40%
Race/Ethnicity, Customized (Count of Participants)
White - White/Caucasian/European Heritage	5 100%	0 NaN	0 NaN	5 100%

Outcome Measures

1. Primary Outcome

Title	Part 1: Number of Participants With Any Non-serious Adverse Event (Non-SAE), Serious AE (SAE), Dose Limiting Toxicities (DLT), Dose Reductions or Delays and Withdrawals Due to Toxicities
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. An event was considered a DLT if it occurred within the first 28 days of treatment, and met the DLT criteria unless it could be clearly established that the event was unrelated to treatment.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population: All participants who received at least one dose of study treatment.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Non-SAEs	5 100%
SAEs	1 20%
DLT	0 0%
Dose reductions or delays	0 0%
Withdrawals due to toxicities	0 0%

2. Primary Outcome

Title	Part 1: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Platelets, Cycle 1, Day 1, n=5	-13.826 (16.2868)
Platelets, Cycle 1, Day 7, n=5	-17.984 (15.7398)
Platelets, Cycle 1, Day 15, n=4	-19.250 (8.2614)
Platelets, Cycle 1, Day 22, n=3	-20.667 (14.3643)
Platelets, Cycle 2, Day 1, n=3	-16.000 (18.7350)
Platelets, Cycle 2, Day 7, n=3	-21.333 (28.3784)
Platelets, Cycle 2, Day 15, n=3	-24.333 (15.3731)
Platelets, Cycle 2, Day 22, n=3	-24.667 (19.3477)
Platelets, Cycle 3, Day 1, n=3	-17.000 (14.1067)
Platelets, Cycle 4, Day 1, n=2	-13.000 (4.2426)
Platelets, Cycle 5, Day 1, n=1	-11.000 (NA)
Neutrophils, Cycle 1, Day 1, n=5	-0.019 (0.1298)
Neutrophils, Cycle 1, Day 7, n=5	0.035 (0.2058)
Neutrophils, Cycle 1, Day 15, n=4	0.060 (0.3282)
Neutrophils, Cycle 1, Day 22, n=3	0.100 (0.1732)
Neutrophils, Cycle 2, Day 1, n=3	0.200 (0.3000)
Neutrophils, Cycle 2, Day 7, n=3	0.300 (0.3606)
Neutrophils, Cycle 2, Day 15, n=3	0.333 (0.3055)
Neutrophils, Cycle 2, Day 22, n=3	0.267 (0.4041)
Neutrophils, Cycle 3, Day 1, n=3	0.267 (0.3215)
Neutrophils, Cycle 4, Day 1, n=2	0.650 (0.2121)
Neutrophils, Cycle 5, Day 1, n=1	0.800 (NA)
Monocytes, Cycle 1, Day 1, n=5	0.017 (0.1359)
Monocytes, Cycle 1, Day 7, n=5	0.059 (0.0853)
Monocytes, Cycle 1, Day 15, n=4	0.100 (0.0816)
Monocytes, Cycle 1, Day 22, n=3	12.633 (21.7086)
Monocytes, Cycle 2, Day 1, n=3	0.267 (0.2517)
Monocytes, Cycle 2, Day 7, n=3	0.400 (0.6083)
Monocytes, Cycle 2, Day 15, n=3	0.633 (0.7095)
Monocytes, Cycle 2, Day 22, n=3	0.267 (0.2517)
Monocytes, Cycle 3, Day 1, n=3	0.300 (0.1732)
Monocytes, Cycle 4, Day 1, n=2	1.000 (0.1414)
Monocytes, Cycle 5, Day 1, n=1	1.600 (NA)
Lymphocytes, Cycle 1, Day 1, n=5	-0.036 (0.0924)
Lymphocytes, Cycle 1, Day 7, n=5	0.008 (0.1761)
Lymphocytes, Cycle 1, Day 15, n=4	-0.073 (0.0486)
Lymphocytes, Cycle 1, Day 22, n=3	-0.033 (0.0577)
Lymphocytes, Cycle 2, Day 1, n=3	-0.067 (0.1528)
Lymphocytes, Cycle 2, Day 7, n=3	-0.033 (0.3055)
Lymphocytes, Cycle 2, Day 15, n=3	0.033 (0.3786)
Lymphocytes, Cycle 2, Day 22, n=3	0.033 (0.2082)
Lymphocytes, Cycle 3, Day 1, n=3	-0.067 (0.3055)
Lymphocytes, Cycle 4, Day 1, n=2	0.200 (0.0000)
Lymphocytes, Cycle 5, Day 1, n=1	0.400 (NA)
Leucocytes, Cycle 1, Day 1, n=5	-0.054 (0.1720)
Leucocytes, Cycle 1, Day 7, n=5	0.154 (0.3257)
Leucocytes, Cycle 1, Day 15, n=4	0.032 (0.3208)
Leucocytes, Cycle 1, Day 22, n=3	0.267 (0.5132)
Leucocytes, Cycle 2, Day 1, n=3	0.433 (0.7234)
Leucocytes, Cycle 2, Day 7, n=3	0.700 (1.3748)
Leucocytes, Cycle 2, Day 15, n=3	1.033 (1.4572)
Leucocytes, Cycle 2, Day 22, n=3	0.633 (0.9292)
Leucocytes, Cycle 3, Day 1, n=3	0.633 (0.9074)
Leucocytes, Cycle 4, Day 1, n=2	2.000 (0.0000)
Leucocytes, Cycle 5, Day 1, n=1	2.900 (NA)
Eosinophils, Cycle 1, Day 1, n=5	-0.000 (0.0009)
Eosinophils, Cycle 1, Day 7, n=5	0.016 (0.0252)
Eosinophils, Cycle 1, Day 15, n=4	-0.008 (0.0150)
Eosinophils, Cycle 1, Day 22, n=3	0.000 (0.0000)
Eosinophils, Cycle 2, Day 1, n=3	0.000 (0.0000)
Eosinophils, Cycle 2, Day 7, n=3	0.000 (0.0000)
Eosinophils, Cycle 2, Day 15, n=3	0.000 (0.0000)
Eosinophils, Cycle 2, Day 22, n=3	0.000 (0.0000)
Eosinophils, Cycle 3, Day 1, n=3	0.000 (0.0000)
Eosinophils, Cycle 4, Day 1, n=2	0.050 (0.0707)
Eosinophils, Cycle 5, Day 1, n=1	0.100 (NA)
Basophils, Cycle 1, Day 1, n=5	0.004 (0.0080)
Basophils, Cycle 1, Day 7, n=5	0.017 (0.0323)
Basophils, Cycle 1, Day 15, n=4	0.003 (0.0050)
Basophils, Cycle 1, Day 22, n=3	0.000 (0.0000)
Basophils, Cycle 2, Day 1, n=3	0.000 (0.0000)
Basophils, Cycle 2, Day 7, n=3	0.000 (0.0000)
Basophils, Cycle 2, Day 15, n=3	0.000 (0.0000)
Basophils, Cycle 2, Day 22, n=3	0.000 (0.0000)
Basophils, Cycle 3, Day 1, n=3	0.000 (0.0000)
Basophils, Cycle 4, Day 1, n=2	0.050 (0.0707)
Basophils, Cycle 5, Day 1, n=1	0.000 (NA)

3. Primary Outcome

Title	Part 1: Change From Baseline in Mean Corpuscular Volume (MCV) at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 1, n=5	-0.280 (1.5450)
Cycle 1, Day 7, n=4	-0.400 (1.9442)
Cycle 1, Day 15, n=3	-0.267 (3.6679)
Cycle 1, Day 22, n=3	0.400 (5.1730)
Cycle 2, Day 1, n=3	1.667 (6.0003)
Cycle 2, Day 7, n=3	3.500 (6.3592)
Cycle 2, Day 15, n=3	2.933 (7.3528)
Cycle 2, Day 22, n=3	2.900 (9.0000)
Cycle 3, Day 1, n=3	2.700 (9.7370)
Cycle 4, Day 1, n=2	6.750 (6.2933)
Cycle 5, Day 1, n=1	8.500 (NA)

4. Primary Outcome

Title	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 1, n=5	-1.100 (2.8679)
Cycle 1, Day 7, n=4	-1.350 (3.3000)
Cycle 1, Day 15, n=3	-0.100 (1.1358)
Cycle 1, Day 22, n=3	0.067 (1.5308)
Cycle 2, Day 1, n=3	0.833 (1.5177)
Cycle 2, Day 7, n=3	1.067 (1.3796)
Cycle 2, Day 15, n=3	0.900 (1.9672)
Cycle 2, Day 22, n=3	0.767 (2.3798)
Cycle 3, Day 1, n=3	0.933 (3.0665)
Cycle 4, Day 1, n=2	1.950 (1.3435)
Cycle 5, Day 1, n=1	2.200 (NA)

5. Primary Outcome

Title	Part 1: Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
MCHC, Cycle 1, Day 1, n=5	-10.400 (29.3053)
MCHC, Cycle 1, Day 7, n=4	-12.500 (35.8190)
MCHC, Cycle 1, Day 15, n=3	0.333 (2.0817)
MCHC, Cycle 1, Day 22, n=3	0.000 (8.1854)
MCHC, Cycle 2, Day 1, n=3	3.667 (6.6583)
MCHC, Cycle 2, Day 7, n=3	-1.000 (12.4900)
MCHC, Cycle 2, Day 15, n=3	0.000 (7.8102)
MCHC, Cycle 2, Day 22, n=3	-2.000 (8.6603)
MCHC, Cycle 3, Day 1, n=3	1.333 (6.0277)
MCHC, Cycle 4, Day 1, n=2	-3.500 (9.1924)
MCHC, Cycle 5, Day 1, n=1	-8.000 (NA)
Hb, Cycle 1, Day 1, n=5	-2.000 (7.0000)
Hb, Cycle 1, Day 7, n=5	-4.200 (11.3666)
Hb, Cycle 1, Day 15, n=4	-5.000 (11.8040)
Hb, Cycle 1, Day 22, n=3	2.000 (2.6458)
Hb, Cycle 2, Day 1, n=3	-3.667 (12.5831)
Hb, Cycle 2, Day 7, n=3	2.000 (13.4536)
Hb, Cycle 2, Day 15, n=3	0.333 (16.5630)
Hb, Cycle 2, Day 22, n=3	-3.000 (5.2915)
Hb, Cycle 3, Day 1, n=3	-2.333 (7.2342)
Hb, Cycle 4, Day 1, n=2	7.000 (4.2426)
Hb, Cycle 5, Day 1, n=1	6.000 (NA)

6. Primary Outcome

Title	Part 1: Change From Baseline in Hematocrit at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 1, n=5	0.001 (0.0334)
Cycle 1, Day 7, n=5	-0.008 (0.0525)
Cycle 1, Day 15, n=4	-0.018 (0.0401)
Cycle 1, Day 22, n=3	0.007 (0.0100)
Cycle 2, Day 1, n=3	-0.014 (0.0396)
Cycle 2, Day 7, n=3	0.007 (0.0448)
Cycle 2, Day 15, n=3	0.002 (0.0520)
Cycle 2, Day 22, n=3	-0.009 (0.0206)
Cycle 3, Day 1, n=3	-0.008 (0.0244)
Cycle 4, Day 1, n=2	0.024 (0.0191)
Cycle 5, Day 1, n=1	0.023 (NA)

7. Primary Outcome

Title	Part 1: Change From Baseline in Erythrocytes at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 1, n=5	0.030 (0.3489)
Cycle 1, Day 7, n=5	-0.058 (0.5363)
Cycle 1, Day 15, n=4	-0.138 (0.3216)
Cycle 1, Day 22, n=3	0.077 (0.0643)
Cycle 2, Day 1, n=3	-0.193 (0.2558)
Cycle 2, Day 7, n=3	-0.017 (0.2996)
Cycle 2, Day 15, n=3	-0.063 (0.3402)
Cycle 2, Day 22, n=3	-0.173 (0.1901)
Cycle 3, Day 1, n=3	-0.160 (0.2425)
Cycle 4, Day 1, n=2	0.060 (0.0141)
Cycle 5, Day 1, n=1	0.000 (NA)

8. Primary Outcome

Title	Part 1: Change From Baseline in Percent Reticulocytes at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	1
Cycle 1, Day 7	0.000 (NA)
Cycle 1, Day 22	-0.100 (NA)
Cycle 2, Day 1	-0.100 (NA)
Cycle 2, Day 7	0.000 (NA)
Cycle 2, Day 15	0.000 (NA)
Cycle 3, Day 1	-0.100 (NA)
Cycle 4, Day 1	-0.100 (NA)

9. Primary Outcome

Title	Part 1: Change From Baseline in Blast/Leukocytes at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Day 1 of Cycle 1 (Cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	1
Mean (Standard Deviation) [Ratio of blasts to leukocytes]	0.000 (NA)

10. Primary Outcome

Title	Part 1: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and Gamma Glutamyl Transferase (GGT) at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
ALT, Cycle 1, Day 1, n=4	-10.000 (18.1292)
ALT Cycle 1, Day 7, n=5	-3.000 (13.5093)
ALT Cycle 1, Day 15, n=4	-6.250 (15.5000)
ALT Cycle 1, Day 22, n=3	1.333 (15.1767)
ALT Cycle 2, Day 1, n=3	3.000 (39.5095)
ALT Cycle 3, Day 1, n=3	3.333 (42.0040)
ALT Cycle 4, Day 1, n=2	33.000 (1.4142)
ALT Cycle 5, Day 1, n=1	3.000 (NA)
ALP, Cycle 1, Day 1, n=4	-4.750 (3.2016)
ALP Cycle 1, Day 7, n=5	-6.800 (10.3053)
ALP Cycle 1, Day 15, n=4	-4.250 (22.3961)
ALP Cycle 1, Day 22, n=3	8.000 (21.6564)
ALP Cycle 2, Day 1, n=3	23.667 (62.5007)
ALP Cycle 3, Day 1, n=3	15.667 (31.3422)
ALP Cycle 4, Day 1, n=2	18.500 (60.1041)
ALP Cycle 5, Day 1, n=1	21.000 (NA)
AST, Cycle 1, Day 1, n=4	-6.750 (14.8633)
AST Cycle 1, Day 7, n=5	-3.200 (9.3381)
AST Cycle 1, Day 15, n=4	-3.250 (17.6517)
AST Cycle 1, Day 22, n=3	3.000 (27.5136)
AST Cycle 2, Day 1, n=3	-0.333 (30.9246)
AST Cycle 3, Day 1, n=3	-3.667 (38.5530)
AST Cycle 4, Day 1, n=2	22.000 (21.2132)
AST Cycle 5, Day 1, n=1	16.000 (NA)
LDH, Cycle 1, Day 1, n=4	4.000 (90.9395)
LDH Cycle 1, Day 7, n=5	-31.200 (47.2515)
LDH Cycle 1, Day 15, n=3	4.000 (22.6053)
LDH Cycle 1, Day 22, n=3	-12.000 (47.5710)
LDH Cycle 2, Day 1, n=3	-18.333 (55.4106)
LDH Cycle 3, Day 1, n=3	-20.667 (62.7402)
LDH Cycle 4, Day 1, n=2	12.500 (3.5355)
LDH Cycle 5, Day 1, n=1	11.000 (NA)
GGT, Cycle 1, Day 1, n=1	-17.000 (NA)
GGT Cycle 1, Day 7, n=2	-7.500 (9.1924)
GGT Cycle 1, Day 22, n=1	0.000 (NA)
GGT Cycle 2, Day 1, n=1	3.000 (NA)
GGT Cycle 3, Day 1, n=1	8.000 (NA)
GGT Cycle 4, Day 1, n=1	5.000 (NA)

11. Primary Outcome

Title	Part 1: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points
Description	Blood samples were collected from participants for evaluation of clinical chemistry parameters including calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Calcium, Cycle 1, Day 1, n=3	-0.008 (0.0520)
Calcium Cycle 1, Day 7, n=4	-0.075 (0.0535)
Calcium Cycle 1, Day 15, n=3	-0.066 (0.0758)
Calcium Cycle 1, Day 22, n=3	-0.033 (0.0624)
Calcium Cycle 2, Day 1, n=3	-0.067 (0.0144)
Calcium Cycle 3, Day 1, n=3	-0.183 (0.1523)
Calcium Cycle 4, Day 1, n=2	-0.050 (0.0700)
Calcium, Cycle 5, Day 1, n=1	-0.050 (NA)
Chloride, Cycle 1, Day 1, n=4	-0.750 (0.5000)
Chloride Cycle 1, Day 7, n=5	0.600 (4.3932)
Chloride Cycle 1, Day 15, n=4	0.250 (2.5000)
Chloride Cycle 1, Day 22, n=3	0.333 (1.1547)
Chloride Cycle 2, Day 1, n=3	0.333 (1.5275)
Chloride Cycle 3, Day 1, n=3	-0.333 (1.5275)
Chloride Cycle 4, Day 1, n=2	0.000 (2.8284)
Chloride, Cycle 5, Day 1, n=1	0.000 (NA)
Glucose, Cycle 1, Day 1, n=4	0.527 (1.9147)
Glucose Cycle 1, Day 7, n=5	-0.333 (1.5357)
Glucose Cycle 1, Day 15, n=4	0.014 (0.7971)
Glucose Cycle 1, Day 22, n=3	0.870 (0.9309)
Glucose Cycle 2, Day 1, n=3	1.924 (2.1037)
Glucose Cycle 3, Day 1, n=3	1.628 (2.8543)
Glucose Cycle 4, Day 1, n=2	1.027 (1.2954)
Glucose, Cycle 5, Day 1, n=1	1.110 (NA)
Potassium, Cycle 1, Day 1, n=4	0.325 (0.5315)
Potassium Cycle 1, Day 7, n=5	0.000 (0.4528)
Potassium Cycle 1, Day 15, n=4	-0.025 (0.4272)
Potassium Cycle 1, Day 22, n=3	0.067 (0.2887)
Potassium Cycle 2, Day 1, n=3	0.067 (0.1528)
Potassium Cycle 3, Day 1, n=3	-0.367 (0.3786)
Potassium Cycle 4, Day 1, n=2	0.050 (0.0707)
Potassium, Cycle 5, Day 1, n=1	0.500 (NA)
Sodium, Cycle 1, Day 1, n=4	-1.750 (1.2583)
Sodium Cycle 1, Day 7, n=5	-1.000 (2.2361)
Sodium Cycle 1, Day 15, n=4	-2.000 (2.4495)
Sodium Cycle 1, Day 22, n=3	-0.667 (2.0817)
Sodium Cycle 2, Day 1, n=3	0.333 (0.5774)
Sodium Cycle 3, Day 1, n=3	-1.000 (5.0000)
Sodium Cycle 4, Day 1, n=2	-0.500 (2.1213)
Sodium, Cycle 5, Day 1, n=1	0.000 (NA)
Urea nitrogen, Cycle 1, Day 1, n=3	2.701 (2.3181)
Urea nitrogen Cycle 1, Day 7, n=4	1.214 (3.4779)
Urea nitrogen Cycle 1, Day 15, n=3	1.547 (3.3171)
Urea nitrogen Cycle 1, Day 22, n=3	1.309 (3.8173)
Urea nitrogen Cycle 2, Day 1, n=3	0.238 (2.1519)
Urea nitrogen Cycle 3, Day 1, n=3	-1.190 (1.7610)
Urea nitrogen Cycle 4, Day 1, n=2	-0.535 (1.2622)
Urea nitrogen, Cycle 5, Day 1, n=1	-1.428 (NA)
Phosphate, Cycle 1, Day 1, n=1	0.194 (NA)
Phosphate Cycle 1, Day 7, n=2	-0.081 (0.1598)
Phosphate Cycle 1, Day 22, n=1	-0.032 (NA)
Phosphate Cycle 2, Day 1, n=1	0.194 (NA)
Phosphate Cycle 3, Day 1, n=1	0.000 (NA)
Phosphate Cycle 4, Day 1, n=1	0.032 (NA)

12. Primary Outcome

Title	Part 1: Change From Baseline in Albumin and Protein at Indicated Time Points
Description	Blood samples were collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Albumin, Cycle 1, Day 1, n=4	-1.250 (2.2174)
Albumin Cycle 1, Day 7, n=4	-1.250 (2.5000)
Albumin Cycle 1, Day 15, n=3	-1.667 (1.5275)
Albumin Cycle 1, Day 22, n=3	-1.333 (0.5774)
Albumin Cycle 2, Day 1, n=3	-1.667 (2.0817)
Albumin Cycle 3, Day 1, n=3	-6.000 (6.2450)
Albumin Cycle 4, Day 1, n=2	0.000 (1.4142)
Albumin Cycle 5, Day 1, n=1	1.000 (NA)
Protein, Cycle 1, Day 1, n=4	-3.250 (3.8622)
Protein Cycle 1, Day 7, n=5	-3.200 (4.3243)
Protein Cycle 1, Day 15, n=4	-1.500 (4.4347)
Protein Cycle 1, Day 22, n=3	-1.667 (1.1547)
Protein Cycle 2, Day 1, n=3	-3.333 (5.8595)
Protein Cycle 3, Day 1, n=3	-7.333 (6.8069)
Protein Cycle 4, Day 1, n=2	-2.000 (2.8284)
Protein Cycle 5, Day 1, n=1	0.000 (NA)

13. Primary Outcome

Title	Part 1: Change From Baseline in Partial Pressure Carbon Dioxide (pCO2) at Indicated Time Points
Description	Blood samples were collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Day 1 of Cycle 1 (cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	1
Mean (Standard Deviation) [Kilopascal]	0.173 (NA)

14. Primary Outcome

Title	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points
Description	Vital signs including SBP and DBP were measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
SBP, Cycle 1, Day 7, n=5	-10.2 (4.76)
SBP, Cycle 1, Day 15, n=4	-13.5 (3.87)
SBP, Cycle 2, Day 1, n=3	-4.7 (3.79)
SBP, Cycle 3, Day 1, n=3	-3.7 (8.39)
SBP, Cycle 4, Day 1, n=2	-5.0 (2.83)
SBP, Cycle 5, Day 1, n=1	-6.0 (NA)
DBP, Cycle 1, Day 7, n=5	-2.6 (8.62)
DBP, Cycle 1, Day 15, n=4	-3.5 (4.04)
DBP, Cycle 2, Day 1, n=3	-7.3 (10.02)
DBP, Cycle 3, Day 1, n=3	2.7 (4.73)
DBP, Cycle 4, Day 1, n=2	3.0 (7.07)
DBP, Cycle 5, Day 1, n=1	-4.0 (NA)

15. Primary Outcome

Title	Part 1: Change From Baseline in Heart Rate at Indicated Time-points
Description	Vital signs including heart rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 7, n=5	4.8 (6.69)
Cycle 1, Day 15, n=4	-2.5 (7.42)
Cycle 2, Day 1, n=3	-6.3 (2.89)
Cycle 3, Day 1, n=3	-1.0 (9.00)
Cycle 4, Day 1, n=2	-2.0 (8.49)
Cycle 5, Day 1, n=1	-1.0 (NA)

16. Primary Outcome

Title	Part 1: Change From Baseline in Respiratory Rate at Indicated Time-points
Description	Vital signs including respiratory rate was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 7, n=5	-0.4 (1.14)
Cycle 1, Day 15, n=4	-0.5 (1.00)
Cycle 2, Day 1, n=3	-1.0 (1.00)
Cycle 3, Day 1, n=3	-0.3 (1.53)
Cycle 4, Day 1, n=2	-0.5 (0.71)
Cycle 5, Day 1, n=1	-1.0 (NA)

17. Primary Outcome

Title	Part 1: Change From Baseline in Body Temperature at Indicated Time-points
Description	Vital signs including body temperature was measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1 (Days 7, 15), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 7, n=5	0.14 (0.279)
Cycle 1, Day 15, n=4	0.10 (0.216)
Cycle 2, Day 1, n=3	0.27 (0.231)
Cycle 3, Day 1, n=3	0.20 (0.300)
Cycle 4, Day 1, n=2	0.10 (0.283)
Cycle 5, Day 1, n=1	-0.20 (NA)

18. Primary Outcome

Title	Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate at Indicated Time-points
Description	Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1 (Days 1, 7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 1, n=2	2.0 (2.83)
Cycle 1, Day 7, n=5	-1.0 (11.94)
Cycle 2, Day 1, n=3	-5.3 (5.51)
Cycle 3, Day 1, n=3	2.3 (10.02)
Cycle 4, Day 1, n=2	-3.0 (9.90)
Cycle 5, Day 1, n=1	-7.0 (NA)

19. Primary Outcome

Title	Part 1: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTc Corrected by Bazett's Formula (QTcB) and QTc Corrected by Fridericia's Formula (QTcF) at Indicated Time-points
Description	Single 12-lead ECG was obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1 (Days 1,7), Cycle 2 (Day 1), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
PR interval, Cycle 1, Day 1, n=2	0.0 (0.00)
PR interval, Cycle 1, Day 7, n=5	39.8 (88.34)
PR interval, Cycle 2, Day 1, n=3	6.0 (9.17)
PR interval, Cycle 3, Day 1, n=3	0.7 (8.08)
PR interval, Cycle 4, Day 1, n=2	6.0 (14.14)
PR interval, Cycle 5, Day 1, n=1	12.0 (NA)
QRS duration, Cycle 1, Day 1, n=2	-1.0 (4.24)
QRS duration, Cycle 1, Day 7, n=5	-17.2 (39.61)
QRS duration, Cycle 2, Day 1, n=3	2.0 (2.00)
QRS duration, Cycle 3, Day 1, n=3	3.3 (1.15)
QRS duration, Cycle 4, Day 1, n=2	-1.0 (1.41)
QRS duration, Cycle 5, Day 1, n=1	-8.0 (NA)
QT interval, Cycle 1, Day 1, n=2	0.0 (0.00)
QT interval, Cycle 1, Day 7, n=5	-5.6 (29.37)
QT interval, Cycle 2, Day 1, n=3	24.7 (18.58)
QT interval, Cycle 3, Day 1, n=3	2.0 (18.00)
QT interval, Cycle 4, Day 1, n=1	-4.0 (NA)
QT interval, Cycle 5, Day 1, n=1	14.0 (NA)
QTcB interval, Cycle 1, Day 1, n=2	7.0 (9.90)
QTcB interval, Cycle 1, Day 7, n=2	-35.5 (82.73)
QTcF interval, Cycle 1, Day 1, n=2	4.5 (6.36)
QTcF interval, Cycle 1, Day 7, n=5	-9.4 (38.12)
QTcF interval, Cycle 2, Day 1, n=3	8.0 (5.57)
QTcF interval, Cycle 3, Day 1, n=3	13.0 (18.52)
QTcF interval, Cycle 4, Day 1, n=2	-6.0 (19.80)
QTcF interval, Cycle 5, Day 1, n=1	-8.0 (NA)

20. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Findings During Physical Examination
Description	A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. This analysis was planned but data was not captured in the database.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	0

21. Primary Outcome

Title	Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)
Description	CBR was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. International Working Group (IWG) criteria, 2006 was to be used to evaluate response.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

22. Primary Outcome

Title	Part 2: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)
Description	Objective response rate was defined as the percentage of participants who achieved CR or PR or mCR or HI prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were to be treated as non-responders. IWG criteria, 2006 was to be used to evaluate response.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

23. Secondary Outcome

Title	Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Clinical Benefit Rate (CBR)
Description	Clinical Benefit Rate was defined as the percentage of participants achieving a confirmed Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) or Stable Disease (SD) prior to new anti-cancer therapy and crossover on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Number (95% Confidence Interval) [Percentage of Participants]	40 800%

24. Secondary Outcome

Title	Part 1: Percentage of Participants With Investigator-assessed Best Response Assessed by Objective Response Rate (ORR)
Description	Objective Response Rate was defined as the percentage of participants who achieved Complete Remission (CR) or Partial Remission (PR) or Marrow Complete Remission (mCR) or confirmed Hematologic Improvement (HI) prior to new anti-cancer therapy on the All Treated Subjects Population. Participants with Not Evaluable or missing response were treated as non-responders. International Working Group (IWG) criteria, 2006 was used to evaluate response.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Number (95% Confidence Interval) [Percentage of Participants]	20 400%

25. Secondary Outcome

Title	Part 1: Plasma Concentration of GSK2879552
Description	Blood samples were collected at indicated time points to evaluate concentration of GSK2879552. Each Pharmacokinetic (PK) sample was collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days. PK Concentration Population consisted of all participants in the All Treated Subject Population for whom a blood sample for pharmacokinetics was obtained and analyzed.
Time Frame	Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

PK Concentration Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Cycle 1, Day 1, pre-dose, n=5	0.00 (NA)
Cycle 1, Day 1, 0.5 hour, n=4	11.79 (9.270)
Cycle 1, Day 1, 1 hour, n=5	8.18 (4.830)
Cycle 1, Day 1, 3 hour, n=5	6.40 (1.990)
Cycle 1, Day 2, pre-dose, n=5	1.03 (0.409)
Cycle 1, Day 4, pre-dose, n=5	1.87 (0.716)
Cycle 1, Day 7, pre-dose, n=5	1.97 (0.553)
Cycle 1, Day 7, 0.5 hour, n=5	9.58 (8.395)
Cycle 1, Day 7, 1 hour, n=5	9.17 (4.4777)
Cycle 1, Day 7, 3 hour, n=5	8.58 (3.595)
Cycle 1, Day 15, pre-dose, n=3	2.00 (0.798)
Cycle 1, Day 15, 0.5-1 hour, n=3	13.39 (0.798)
Cycle 1, Day 22, pre-dose, n=3	1.89 (0.723)
Cycle 2, Day 1, pre-dose, n=3	2.16 (0.843)
Cycle 2, Day 7, pre-dose, n=3	1.81 (0.585)
Cycle 2, Day 15, pre-dose, n=3	2.33 (1.135)
Cycle 2, Day 22, pre-dose, n=3	2.11 (0.709)
Cycle 3, Day 1, pre-dose, n=3	1.99 (0.802)
Cycle 4, Day 1, pre-dose, n=2	1.63 (0.085)
Cycle 5, Day 1, pre-dose, n=1	1.97 (NA)

26. Secondary Outcome

Title	Part 1: Plasma Concentration of Azacitidine
Description	Blood samples were to be collected at indicated time points to evaluate concentration of Azacitidine.
Time Frame	Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Days 2,4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3,4,5 (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

PK Concentration Population. Data was not collected due to blood samples were not collected as participants were not enrolled in GSK2879552 + Azacitidine arm due to early termination of the study.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	0

27. Secondary Outcome

Title	Part 1: Duration of Response
Description	Duration of response is defined as the subset of participants (responders) who show a response (CR, mCR, PR, or HI), the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the DOR was to be censored at last disease assessment.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as DOR could not be calculated because of the early termination of the study did not allow for this endpoint to be observed.

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	0

28. Secondary Outcome

Title	Part 1: Progression-free Survival
Description	Progression-free survival (PFS) is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was censored at the date of the last adequate assessment.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Median (95% Confidence Interval) [Weeks]	22.4

29. Secondary Outcome

Title	Part 1: Overall Survival
Description	Overall survival (OS) is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival (OS), 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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Median (95% Confidence Interval) [Weeks]	22.4

30. Secondary Outcome

Title	Part 1: Proportion of Participants With Disease Progression to Acute Myeloblastic Leukemia (AML)
Description	The proportion of participants with disease progression to AML is defined as the percentage of participants experiencing AML on the All Treated Subjects Population.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Number [Percentage of Participants]	40 800%

31. Secondary Outcome

Title	Part 1: Time to AML Progression
Description	Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Median (95% Confidence Interval) [Weeks]	22.4

32. Secondary Outcome

Title	Part 1: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month
Description	Number of participants with documented platelet and RBC transfusions have been presented.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Platelets transfusion	5 100%
RBC transfusion	4 80%
RBC concentrated transfusion	1 20%

33. Secondary Outcome

Title	Part 2: Number of Participants With Any AEs and SAEs
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

34. Secondary Outcome

Title	Part 2: Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

35. Secondary Outcome

Title	Part 2: Change From Baseline in MCV at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including MCV. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

36. Secondary Outcome

Title	Part 2: Change From Baseline in MCH at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including MCH. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

37. Secondary Outcome

Title	Part 2: Change From Baseline in MCHC and Hb at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including MCHC and Hb. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

38. Secondary Outcome

Title	Part 2: Change From Baseline in Hematocrit at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including Hematocrit. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

39. Secondary Outcome

Title	Part 2: Change From Baseline in Erythrocytes at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including erythrocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

40. Secondary Outcome

Title	Part 2: Change From Baseline in Percent Reticulocytes at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including percent reticulocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

41. Secondary Outcome

Title	Part 2: Change From Baseline in Blast/Leukocytes at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of hematology parameters including blast/leukocytes. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

42. Secondary Outcome

Title	Part 2: Change From Baseline in ALT, ALP, AST, LDH and GGT at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including ALT, ALP, AST, LDH and GGT. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

43. Secondary Outcome

Title	Part 2: Change From Baseline in Calcium, Chloride, Glucose, Potassium, Sodium, Phosphate and Urea Nitrogen at Indicated Time-points
Description	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Calcium, chloride, glucose, potassium, sodium, phosphate and urea nitrogen. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

44. Secondary Outcome

Title	Part 2: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points
Description	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

45. Secondary Outcome

Title	Part 2: Change From Baseline in Albumin and Protein at Indicated Time Points
Description	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including Albumin and Protein. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

46. Secondary Outcome

Title	Part 2: Change From Baseline in pCO2 at Indicated Time Points
Description	Blood samples were to be collected from participants for evaluation of clinical chemistry parameters including pCO2. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

47. Secondary Outcome

Title	Part 2: Change From Baseline in SBP and DBP at Indicated Time-points
Description	Vital signs including SBP and DBP were to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

48. Secondary Outcome

Title	Part 2: Change From Baseline in Heart Rate at Indicated Time-points
Description	Vital signs including heart rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

49. Secondary Outcome

Title	Part 2: Change From Baseline in Respiratory Rate at Indicated Time-points
Description	Vital signs including respiratory rate was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

50. Secondary Outcome

Title	Part 2: Change From Baseline in Body Temperature at Indicated Time-points
Description	Vital signs including body temperature was to be measured after resting for at least 5 minutes in a semi-supine position. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

51. Secondary Outcome

Title	Part 2: Change From Baseline in ECG Mean Heart Rate at Indicated Time-points
Description	Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

52. Secondary Outcome

Title	Part 2: Change From Baseline in ECG PR Interval, QRS Duration, QT Interval, QTcB and QTcF at Indicated Time-points
Description	Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was to be calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

53. Secondary Outcome

Title	Part 2: Number of Participants With Abnormal Findings During Physical Examination
Description	A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. A brief physical examination included, at a minimum assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

54. Secondary Outcome

Title	Part 2: Plasma Clearance (CL/F) of GSK2879552
Description	Blood samples were to be collected at indicated time points to evaluate CL/F of GSK2879552. Each PK sample was to be collected as close as possible to the planned time relative to the dose (i.e., time zero) administered to the participant on PK days.
Time Frame	Cycle 1, Day 1: pre-dose, 0.5, 1, 3 hour; pre-dose on Day 4; Day 7: pre-dose, 0.5, 1, 3 hour; Day 15: pre-dose, 0.5-1 hour post-dose; pre-dose on Day 22; Cycle 2: pre-dose on Days 1, 7, 15, 22; Pre-dose on Day 1 of Cycles 3 to 1 (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

PK Concentration Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

55. Secondary Outcome

Title	Part 2: Duration of Response
Description	Duration of response is defined as the time from first documented evidence of response until the first documented sign of disease progression or death. If no disease progression or death, the duration of response was to be censored at last disease assessment.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

56. Secondary Outcome

Title	Part 2: Progression-free Survival
Description	Progression-free survival is defined as the time from first treatment dose until the first documented sign of disease progression or death. If the participant missed more than one visit prior to the date of documented events, PFS was to be censored at the last adequate assessment prior to missing. Otherwise, if the participant did not have a documented date of events, PFS was to be censored at the date of the last adequate assessment.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

57. Secondary Outcome

Title	Part 2: Overall Survival
Description	Overall survival is defined as the time from first treatment dose until death due to any reason. For the analysis of overall survival, the last date of known contact was to be used for those participants who had not died at the time of analysis; such participants were to be considered censored.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

58. Secondary Outcome

Title	Part 2: Percentage of Participants With Disease Progression to AML
Description	The percentage of participants experiencing AML on the All Treated Subjects Population was to be presented.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

59. Secondary Outcome

Title	Part 2: Time to AML Progression
Description	Time to AML progression is defined as the time from first treatment dose until AML progression or crossover if using the All Treated Subjects Population. For the analysis of time to AML, if the participant did not experience AML, time to AML was to be censored at the last treatment prior to the initiation of anti-cancer therapy or crossover.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

60. Secondary Outcome

Title	Part 2: Number of Participants With Documented Platelet and Red Blood Cell (RBC) Transfusions Per Month
Description	Number of participants with documented platelet and RBC transfusions were to be presented.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Data was not collected for this endpoint as study was terminated during Part 1 and Part 2 was not initiated.

Arm/Group Title	Part 2: GSK2879552	Part 2: GSK2879552+Azacitidine
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.	Part 2 was to be initiated once Part 1 is completed and dose has been selected for GSK2879552 monotherapy and combination of azacitidine with GSK2879552. Treatment with GSK2879552 in this combination therapy arm was to be administered orally once a day at RP2D as continuous daily dosing in each cycle (of 28 days) until disease progression in Part 2 of the study. Azacitidine was to be administered at 75 milligram per meter^2 on Days 1-7 of each 28 day cycle by intravenous (IV) infusion or subcutaneous (SC) injection (route of administration: by physicians choice).
Measure Participants	0	0

61. Primary Outcome

Title	Part 1: Change From Baseline in Total Bilirubin, Direct Bilirubin, Creatinine and Urate at Indicated Time Points
Description	Blood samples were collected from participants for evaluation of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Creatinine and urate. Baseline was defined as the value obtained prior to first dosing (Day 1). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Time Frame	Baseline and Cycle 1(Days 1, 7, 15, 22), Cycle 2 (Days 1, 7, 15 ,22), Cycle 3 (Day 1), Cycle 4 (Day 1), Cycle 5 (Day 1) (each cycle of 28 days)

Outcome Measure Data

Analysis Population Description

All Treated Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
Measure Participants	5
Total Bilirubin, Cycle 1, Day 1, n=4	-3.420 (5.4075)
Total Bilirubin Cycle 1, Day 7, n=5	-1.094 (5.6580)
Total Bilirubin Cycle 1, Day 15, n=4	0.128 (6.6278)
Total Bilirubin Cycle 1, Day 22, n=3	-1.710 (2.9618)
Total Bilirubin Cycle 2, Day 1, n=3	-2.850 (3.5596)
Total Bilirubin Cycle 3, Day 1, n=3	0.000 (3.4200)
Total Bilirubin Cycle 4, Day 1, n=2	-0.855 (3.6275)
Total Bilirubin, Cycle 5, Day 1, n=1	-3.420 (NA)
Direct Bilirubin, Cycle 1, Day 1, n=1	1.368 (NA)
Creatinine, Cycle 1, Day 1, n=4	16.133 (25.5329)
Creatinine Cycle 1, Day 7, n=5	4.066 (11.2271)
Creatinine Cycle 1, Day 15, n=4	17.238 (17.4800)
Creatinine Cycle 1, Day 22, n=3	23.279 (18.5500)
Creatinine Cycle 2, Day 1, n=3	16.501 (16.6402)
Creatinine Cycle 3, Day 1, n=3	15.912 (20.5613)
Creatinine Cycle 4, Day 1, n=2	32.708 (8.7512)
Creatinine, Cycle 5, Day 1, n=1	4.420 (NA)
Urate, Cycle 1, Day 1, n=1	41.636 (NA)
Urate Cycle 1, Day 7, n=2	5.948 (0.0000)
Urate Cycle 1, Day 22, n=1	35.688 (NA)
Urate Cycle 2, Day 1, n=1	65.428 (NA)
Urate Cycle 3, Day 1, n=1	89.220 (NA)
Urate Cycle 4, Day 1, n=1	59.480 (NA)

Adverse Events

Time Frame	Serious adverse events (SAEs) and Non-serious adverse events (Non-SAEs) were collected from the start of the study treatment up to Cycle 5 (each cycle of 28 days) in Part 1.
Adverse Event Reporting Description	SAEs and Non-SAEs were reported by treatment for the All Treated Subjects Population which comprised of all participants who received at least one dose of study treatment. Data is presented for Part 1 only as data was not collected in Part 2 due to the study was terminated during Part 1 only, and Part 2 was not initiated.
Arm/Group Title	Part 1: GSK2879552
Arm/Group Description	Participants in this monotherapy arm were administered with GSK2879552 0.5 milligrams or 2 milligrams oral capsules once a day as continuous daily dosing in each cycle (of 28 days) until disease progression during Part 1 of the study.
All Cause Mortality
	Part 1: GSK2879552
	Affected / at Risk (%)	# Events
Total	2/5 (40%)
Serious Adverse Events
	Part 1: GSK2879552
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Infections and infestations
Sinusitis	1/5 (20%)
Injury, poisoning and procedural complications
Subdural haematoma	1/5 (20%)
Transfusion reaction	1/5 (20%)
Other (Not Including Serious) Adverse Events
	Part 1: GSK2879552
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anaemia	1/5 (20%)
Increased tendency to bruise	1/5 (20%)
Leukopenia	1/5 (20%)
Cardiac disorders
Atrial fibrillation	1/5 (20%)
Gastrointestinal disorders
Diarrhoea	1/5 (20%)
Dyspepsia	1/5 (20%)
Gastrooesophageal reflux disease	1/5 (20%)
Gingival bleeding	1/5 (20%)
General disorders
Fatigue	3/5 (60%)
Oedema	1/5 (20%)
Pyrexia	1/5 (20%)
Infections and infestations
Fungal infection	1/5 (20%)
Staphylococcal infection	1/5 (20%)
Investigations
Weight decreased	1/5 (20%)
White blood cell count decreased	1/5 (20%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)
Fluid overload	1/5 (20%)
Hypokalaemia	1/5 (20%)
Tumour lysis syndrome	1/5 (20%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)
Back pain	1/5 (20%)
Nervous system disorders
Balance disorder	1/5 (20%)
Dizziness	1/5 (20%)
Parosmia	1/5 (20%)
Syncope	1/5 (20%)
Psychiatric disorders
Anxiety	1/5 (20%)
Insomnia	1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional	1/5 (20%)
Rhinorrhoea	1/5 (20%)
Skin and subcutaneous tissue disorders
Rash	2/5 (40%)
Blood blister	1/5 (20%)
Eczema	1/5 (20%)
Vascular disorders
Hypotension	1/5 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.