Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

A Phase I/II Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents in Participants With Myelodysplastic Syndrome and Acute Myeloid Leukaemia

This study will evaluate the safety, tolerability, and clinical activity of GSK3326595 in participants with relapsed and refractory MDS, chronic myelomonocytic leukemia (CMML), and AML. The study will be conducted in 2 parts: Part 1 will determine the clinical benefit rate (CBR) of GSK3326595 in monotherapy and Part 2 will be expanded to study GSK3326595 in combination with 5-Azacitidine which will be composed of a dose escalation phase followed by dose expansion cohort of GSK3326595.

Study Overview

• Status: Terminated
• Conditions: Neoplasms
• Intervention / Treatment: Drug: GSK3326595; Drug: 5-Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • GSK Investigational Site
  • Florida
    • Miami, Florida, United States, 33136
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • GSK Investigational Site
    • Boston, Massachusetts, United States, 02215
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10065
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained).
• Diagnosis of MDS, CMML or AML
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
• Adequate organ function
• A woman of childbearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test within 7 days before the first dose of study intervention.

Exclusion Criteria:

• History of, or known, central nervous system (CNS) involvement
• Prior solid organ transplantation
• Known allergies, hypersensitivity, or intolerance to GSK3326595 or 5-Azacitidine or its excipient
• Prior therapy with any Protein arginine methyl transferase 5 (PRMT5) inhibitor
• History of a second malignancy, excluding non-melanoma skin cell cancer, within the last three years
• Active severe or uncontrolled infection
• History of optic nerve neuropathy or neuritis.
• History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: Participants receiving GSK3326595	Drug: GSK3326595; GSK3326595 will be administered.
EXPERIMENTAL: Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine	Drug: GSK3326595; GSK3326595 will be administered.; Drug: 5-Azacitidine; 5-Azacitidine will be administered.
EXPERIMENTAL: Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine	Drug: GSK3326595; GSK3326595 will be administered.; Drug: 5-Azacitidine; 5-Azacitidine will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Percentage of Participants With Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants achieving a complete remission (CR), complete marrow remission (mCR), partial remission (PR), stable disease (SD) lasting at least 8 weeks, or hematologic improvement (HI), per International Working Group (IWG) criteria, where CR=Bone marrow:<=5 percent(%) myeloblasts with normal maturation of all cell lines; PR=Bone marrow blasts decreased by >=50% over pre-treatment but still >5%; mCR=Bone marrow: <=5% myeloblasts and decrease by >=50% over pre-treatment; SD= Failure to achieve at least PR, but no evidence of progression >8 weeks; HI=Erythroid (E): hemoglobin increase of >1.5 grams per deciliter (g/dL), HI-Platelet: increase of >30,000/milliliter (mL) (starting with >20,000/mL) and increase from <20,000/mL to >20,000/mL by >100%; HI-Neutrophil: increase of >100% and >500/microliter. Percentage values are rounded off.	Up to 30.8 months
Part 2: Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment Emergent Adverse Events (STEAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. Treatment emergent adverse event (TEAE) is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with non-STEAEs and STEAEs were planned to be assessed.	Up to 3 years and 2 months
Part 2: Number of Participants With AEs by Severity	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with AEs by severity were planned to be assessed.	Up to 3 years and 2 months
Part 2: Number of Participants With Dose Limiting Toxicities (DLTs)	An event is considered to be a DLT if the event occurs within the first 28 days of treatment meeting one of the following criteria of toxicity, Hematologic: Grade 4 or greater treatment-emergent neutropenia, anemia, or thrombocytopenia, lasting for >=14 days in the absence of Investigational Product, that cannot be attributed to underlying disease as described in National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4; Non-hematologic: Hepatic toxicity that meets Liver Stopping Criteria, Grade 3 nausea, vomiting or diarrhea that does not improve within 72 hours despite appropriate supportive treatments, Grade 4 or greater nausea, vomiting, or diarrhea of any duration, Any other Grade 3 or greater clinically significant non-hematologic toxicity; Other: Inability to receive all planned doses, dose interruption and Grade 2 or higher toxicity. Number of participants with DLTs were planned to be assessed.	Up to 28 days
Part 2: Number of Participants With AEs Leading to Dose Interruptions, Dose Reductions and Treatment Discontinuation Due to AEs	Number of participants with AEs leading to dose interruptions, dose reductions and treatment discontinuation due to AEs were planned to be assessed.	Up to 3 years and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Common Non-STEAEs and STEAEs	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs which were not serious, were considered as non-STEAEs.	Up to 30.8 months
Part 1: Number of Participants With AEs by Severity	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity of each AE was reported during the study and was assigned a grade according to the NCI-CTCAE. AEs severity were graded as: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences and Grade 5=death related to AE.	Up to 30.8 months
Part 1: Number of Participants With DLTs	An event is considered to be a DLT if the event occurs within the first 28 days of treatment meeting one of the following criteria of toxicity, Hematologic: Grade 4 or greater treatment-emergent neutropenia, anemia, or thrombocytopenia, lasting for >=14 days in the absence of Investigational Product, that cannot be attributed to underlying disease as described in NCI-CTCAE version 4; Non-hematologic: Hepatic toxicity that meets Liver Stopping Criteria, Grade 3 nausea, vomiting or diarrhea that does not improve within 72 hours despite appropriate supportive treatments, Grade 4 or greater nausea, vomiting, or diarrhea of any duration, Any other Grade 3 or greater clinically significant non-hematologic toxicity; Other: Inability to receive all planned doses, dose interruption and Grade 2 or higher toxicity.	Up to 28 days
Part 1: Overall Response Rate	Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria, where CR=Bone marrow: <=5% myeloblasts with normal maturation of all cell lines; PR=Bone marrow blasts decreased by >=50% over pre-treatment but still >5%; mCR= Bone marrow: ≤ 5% myeloblasts and decrease by >=50% over pre-treatment. Percentage values are rounded off.	Up to 30.8 months
Part 1: Progression Free Survival	Progression free survival is defined as time from first dose to disease progression, as defined by IWG criteria, or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.	Up to 30.8 months
Part 1: Overall Survival	Overall survival is defined as time from first dose to death due to any cause.	Up to 30.8 months
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 Following Administration of Single Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Cmax of GSK3326595 Following Administration of Repeat Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Time of Maximum Concentration Observed (Tmax) of GSK3326595 Following Administration of Single Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Tmax of GSK3326595 Following Administration of Repeat Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Apparent Terminal Phase Half-life (t1/2) of GSK3326595 Following Administration of Single Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: t1/2 of GSK3326595 Following Administration of Repeat Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Area Under Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within Participant Across All Treatments (AUC[0-t]) of GSK3326595 Following Administration of Single Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: AUC(0-t) of GSK3326595 Following Administration of Repeat Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: AUC From 0 Hours to the Time of Next Dosing (AUC[0-tau]) of GSK3326595	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of GSK3326595 Following Administration of Single Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: AUC(0-inf) of GSK3326595 Following Administration of Repeat Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Oral Clearance (CL/F) of GSK3326595 Following Administration of Single Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: CL/F of GSK3326595 Following Administration of Repeat Dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 15:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 1: Time Invariance Following Administration of GSK3326595	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595. Time invariance was calculated as the ratio of AUC(0-24) on Day 15 divided by AUC(0-infinity) on Day 1 for GSK3326595.	Days1and15:Pre-dose(within 1hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hour(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour),24hours(+/-2hour)post-dose
Part 1: Accumulation Ratio Following Administration of GSK3326595	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595. Accumulation ratio was calculated as the ratio of AUC(0-24) on Day 15 divided by AUC(0-24) on Day 1 for GSK3326595.	Days1and15:Pre-dose(within 1hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hour(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour),24hours(+/-2hour)post-dose
Part 2: Complete Remission (CR) Rate	Complete remission rate is defined as percentage of participants achieving a CR per IWG criteria.	Up to 3 years and 2 months
Part 2: Cmax of GSK3326595 Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: Cmax of GSK3326595 Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: Cmax of 5-Azacitidine Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: Cmax of 5-Azacitidine Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: Tmax of GSK3326595 Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: Tmax of GSK3326595 Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: Tmax of 5-Azacitidine Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: Tmax of 5-Azacitidine Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: t1/2 of GSK3326595 Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: t1/2 of GSK3326595 Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: t1/2 of 5-Azacitidine Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: t1/2 of 5-Azacitidine Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: AUC(0-t) of GSK3326595 Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: AUC(0-t) of GSK3326595 Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: AUC(0-t) of 5-Azacitidine Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: AUC(0-t) of 5-Azacitidine Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: AUC(0-inf) of GSK3326595 Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: AUC(0-inf) of GSK3326595 Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: AUC(0-inf) of 5-Azacitidine Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: AUC(0-inf) of 5-Azacitidine Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: AUC(0-tau) Following Administration of GSK3326595	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: AUC(0-tau) Following Administration of 5-Azacitidine	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: CL/F of GSK3326595 Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: CL/F of GSK3326595 Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: CL/F of 5-Azacitidine Following Administration of Single Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 1:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: CL/F of 5-Azacitidine Following Administration of Repeat Dose	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Day 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: Time Invariance Following Administration of GSK3326595	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Days 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour)post-dose
Part 2: Time Invariance Following Administration of 5-Azacitidine	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Days 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: Accumulation Ratio Following Administration of GSK3326595	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.	Day 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute),12hours(+/-2hour), 24hours(+/-2hour) post-dose
Part 2: Accumulation Ratio Following Administration of 5-Azacitidine	Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of 5-Azacitidine.	Days 1 and 8:Pre-dose(within 1 hour prior to dosing),5minute(+/-2minute),30minute(+/-5minute),1hour(+/-5minute),2hours(+/-5minute),3hours(+/-5minute),4hours(+/-10minute),6hours(+/-10minute),8hours(+/-15minute) post-dose
Part 2: Overall Response Rate	Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria.	Up to 3 years and 2 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 16, 2018
• Primary Completion (ACTUAL): January 11, 2022
• Study Completion (ACTUAL): January 11, 2022

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (ACTUAL): August 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Myelodysplastic syndrome; Acute myeloid leukemia; Chronic myelomonocytic leukemia; GSK3326595; 5-Azacitidine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine; GSK-3326595
• Other Study ID Numbers: 208809

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No