Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Azacitidine

Antimetabolites

Enzyme Inhibitors

Subjects will receive GSK2879552 2 milligrams (mg) once daily in each 28 day cycle.

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.

GSK2879552 will be administered orally as continuous daily dosing.

GSK2879552

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.

GSK Clinical Trials

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.

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

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)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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 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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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

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.

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

Parexel

GlaxoSmithKline

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.

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 1: GSK2879552

Part 2: GSK2879552

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).

Part 2: GSK2879552+Azacitidine

Total

Part 1 data is presented as study was terminated during Part 1 and hence Part 2 was not initiated.

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

GSK Response Center

Non-SAEs

SAEs

Dose reductions or delays

Withdrawals due to toxicities

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

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

Platelets, Cycle 1, Day 1, n=5

Platelets, Cycle 1, Day 7, n=5

Platelets, Cycle 1, Day 15, n=4

Platelets, Cycle 1, Day 22, n=3

Platelets, Cycle 2, Day 1, n=3

Platelets, Cycle 2, Day 7, n=3

Platelets, Cycle 2, Day 15, n=3

Platelets, Cycle 2, Day 22, n=3

Platelets, Cycle 3, Day 1, n=3

Platelets, Cycle 4, Day 1, n=2

Platelets, Cycle 5, Day 1, n=1

Neutrophils, Cycle 1, Day 1, n=5

Neutrophils, Cycle 1, Day 7, n=5

Neutrophils, Cycle 1, Day 15, n=4

Neutrophils, Cycle 1, Day 22, n=3

Neutrophils, Cycle 2, Day 1, n=3

Neutrophils, Cycle 2, Day 7, n=3

Neutrophils, Cycle 2, Day 15, n=3

Neutrophils, Cycle 2, Day 22, n=3

Neutrophils, Cycle 3, Day 1, n=3

Neutrophils, Cycle 4, Day 1, n=2

Neutrophils, Cycle 5, Day 1, n=1

Monocytes, Cycle 1, Day 1, n=5

Monocytes, Cycle 1, Day 7, n=5

Monocytes, Cycle 1, Day 15, n=4

Monocytes, Cycle 1, Day 22, n=3

Monocytes, Cycle 2, Day 1, n=3

Monocytes, Cycle 2, Day 7, n=3

Monocytes, Cycle 2, Day 15, n=3

Monocytes, Cycle 2, Day 22, n=3

Monocytes, Cycle 3, Day 1, n=3

Monocytes, Cycle 4, Day 1, n=2

Monocytes, Cycle 5, Day 1, n=1

Lymphocytes, Cycle 1, Day 1, n=5

Lymphocytes, Cycle 1, Day 7, n=5

Lymphocytes, Cycle 1, Day 15, n=4

Lymphocytes, Cycle 1, Day 22, n=3

Lymphocytes, Cycle 2, Day 1, n=3

Lymphocytes, Cycle 2, Day 7, n=3

Lymphocytes, Cycle 2, Day 15, n=3

Lymphocytes, Cycle 2, Day 22, n=3

Lymphocytes, Cycle 3, Day 1, n=3

Lymphocytes, Cycle 4, Day 1, n=2

Lymphocytes, Cycle 5, Day 1, n=1

Leucocytes, Cycle 1, Day 1, n=5

Leucocytes, Cycle 1, Day 7, n=5

Leucocytes, Cycle 1, Day 15, n=4

Leucocytes, Cycle 1, Day 22, n=3

Leucocytes, Cycle 2, Day 1, n=3

Leucocytes, Cycle 2, Day 7, n=3

Leucocytes, Cycle 2, Day 15, n=3

Leucocytes, Cycle 2, Day 22, n=3

Leucocytes, Cycle 3, Day 1, n=3

Leucocytes, Cycle 4, Day 1, n=2

Leucocytes, Cycle 5, Day 1, n=1

Eosinophils, Cycle 1, Day 1, n=5

Eosinophils, Cycle 1, Day 7, n=5

Eosinophils, Cycle 1, Day 15, n=4

Eosinophils, Cycle 1, Day 22, n=3

Eosinophils, Cycle 2, Day 1, n=3

Eosinophils, Cycle 2, Day 7, n=3

Eosinophils, Cycle 2, Day 15, n=3

Eosinophils, Cycle 2, Day 22, n=3

Eosinophils, Cycle 3, Day 1, n=3

Eosinophils, Cycle 4, Day 1, n=2

Eosinophils, Cycle 5, Day 1, n=1

Basophils, Cycle 1, Day 1, n=5

Basophils, Cycle 1, Day 7, n=5

Basophils, Cycle 1, Day 15, n=4

Basophils, Cycle 1, Day 22, n=3

Basophils, Cycle 2, Day 1, n=3

Basophils, Cycle 2, Day 7, n=3

Basophils, Cycle 2, Day 15, n=3

Basophils, Cycle 2, Day 22, n=3

Basophils, Cycle 3, Day 1, n=3

Basophils, Cycle 4, Day 1, n=2

Basophils, Cycle 5, Day 1, n=1

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).

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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