AzTrials
AzTrials

NeoplasmsPhase 1/2NCT03614728

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 1/2 study testing GSK3326595 and 5-Azacitidine in people with Neoplasms, run by GlaxoSmithKline at 8 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
GSK3326595 and 5-Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
8 sitesin 2 countries
Study dates
16 Oct 2018to 11 Jan 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States7 sites

  • GSK Investigational Site

    Birmingham, Alabama, 35294-3300

  • GSK Investigational Site

    Boston, Massachusetts, 02114

  • GSK Investigational Site

    Boston, Massachusetts, 02215

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Miami, Florida, 33136

  • GSK Investigational Site

    Milwaukee, Wisconsin, 53226

  • GSK Investigational Site

    New York, New York, 10065

Other trials in United States

Canada1 site

  • GSK Investigational Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: 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.

Conditions
Neoplasms
Being tested
GSK3326595, 5-Azacitidine
Keywords
Acute myeloid leukemia, Myelodysplastic syndrome, Chronic myelomonocytic leukemia, GSK3326595, 5-Azacitidine
Medical subject headings
Neoplasms, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3326595Drug

    GSK3326595 will be administered.

  • 5-AzacitidineDrug

    5-Azacitidine will be administered.

Study groups in NCT03614728
Study groupRoleWhat they receive
Part 1: Participants receiving GSK3326595ExperimentalNot described
Receives: Drug: GSK3326595
Part 2 Dose escalation : Participants receiving GSK3326595+5-AzacitidineExperimentalNot described
Receives: Drug: GSK3326595; Drug: 5-Azacitidine
Part 2 Dose expansion: Participants receiving GSK3326595+5-AzacitidineExperimentalNot described
Receives: Drug: GSK3326595; Drug: 5-Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 30.8 months

  2. 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.

    Measured: Up to 3 years and 2 months

  3. 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.

    Measured: Up to 3 years and 2 months

  4. 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.

    Measured: Up to 28 days

  5. 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.

    Measured: Up to 3 years and 2 months

Secondary outcomes (53)

  1. 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.

    Measured: Up to 30.8 months

  2. 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.

    Measured: Up to 30.8 months

  3. 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.

    Measured: Up to 28 days

  4. 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.

    Measured: Up to 30.8 months

  5. 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.

    Measured: Up to 30.8 months

  6. Part 1: Overall Survival

    Overall survival is defined as time from first dose to death due to any cause.

    Measured: Up to 30.8 months

  7. 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.

    Measured: 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

  8. Part 1: Cmax of GSK3326595 Following Administration of Repeat Dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

    Measured: 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

  9. 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.

    Measured: 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

  10. Part 1: Tmax of GSK3326595 Following Administration of Repeat Dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

    Measured: 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

  11. 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.

    Measured: 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

  12. Part 1: t1/2 of GSK3326595 Following Administration of Repeat Dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

    Measured: 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

  13. 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.

    Measured: 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

  14. 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.

    Measured: 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

  15. 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.

    Measured: 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

  16. 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.

    Measured: 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

  17. 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.

    Measured: 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

  18. 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.

    Measured: 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

  19. Part 1: CL/F of GSK3326595 Following Administration of Repeat Dose

    Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595.

    Measured: 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

  20. 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.

    Measured: 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

  21. 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.

    Measured: 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

  22. Part 2: Complete Remission (CR) Rate

    Complete remission rate is defined as percentage of participants achieving a CR per IWG criteria.

    Measured: Up to 3 years and 2 months

  23. 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.

    Measured: 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

  24. 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.

    Measured: 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

  25. 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.

    Measured: 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

  26. 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.

    Measured: 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

  27. 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.

    Measured: 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

  28. 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.

    Measured: 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

  29. 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.

    Measured: 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

  30. 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.

    Measured: 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

  31. 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.

    Measured: 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

  32. 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.

    Measured: 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

  33. 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.

    Measured: 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

  34. 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.

    Measured: 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

  35. 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.

    Measured: 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

  36. 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.

    Measured: 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

  37. 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.

    Measured: 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

  38. 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.

    Measured: 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

  39. 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.

    Measured: 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

  40. 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.

    Measured: 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

  41. 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.

    Measured: 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

  42. 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.

    Measured: 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

  43. 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.

    Measured: 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

  44. 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.

    Measured: 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

  45. 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.

    Measured: 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

  46. 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.

    Measured: 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

  47. 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.

    Measured: 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

  48. 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.

    Measured: 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

  49. Part 2: Time Invariance Following Administration of GSK3326595

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.

    Measured: 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

  50. 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.

    Measured: 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

  51. Part 2: Accumulation Ratio Following Administration of GSK3326595

    Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3326595.

    Measured: 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

  52. 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.

    Measured: 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

  53. Part 2: Overall Response Rate

    Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria.

    Measured: Up to 3 years and 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2018
  2. Study start16 Oct 2018
  3. Primary completion11 Jan 2022
  4. Study completion11 Jan 2022

Why it stopped: Trial terminated due to internal review of clinical data in context of indication under investigation

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
This is an open-label, multicenter, multi-part study.
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03614728
Sponsor's protocol ID
208809
Status last verified
Jan 2023
First submitted
30 Jul 2018
Last updated
6 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Watts J, Minden MD, Bachiashvili K, Brunner AM, Abedin S, Crossman T, Zajac M, Moroz V, Egger JL, Tarkar A, Kremer BE, Barbash O, Borthakur G. Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms. Ther Adv Hematol. 2024 Sep 14;15:20406207241275376. doi: 10.1177/20406207241275376. eCollection 2024.

    PubMed 39290981

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GSK3326595 and 5-Azacitidine in people with Neoplasms, run by GlaxoSmithKline at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) (time frame: Up to 30.8 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03614728, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.

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