Last updated: 01/06/2023 14:40:16

Study to investigate the safety and clinical activity of GSK3326595 and other agents to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML)

GSK study ID
208809
See study documents
Clinicaltrials.gov ID
NCT03614728
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Part 1: Percentage of participants with clinical benefit rate (CBR)

Timeframe: Up to 6 years

Part 2 Dose escalation: Number of participants with adverse events and serious adverse events (AEs and SAEs)

Timeframe: Up to 6 years

Part 2 Dose escalation: Number of participants achieving dose limiting toxicities (DLTs)

Timeframe: Up to 28 days

Part 2 Dose escalation: Number of participants with dose interruptions, dose reductions and treatment discontinuation due to adverse events.

Timeframe: Up to 6 years

Part 2 Dose expansion: Number of participants achieving CR

Timeframe: Up to 6 years

Secondary outcomes:

Part 1 and Part 2 Dose expansion: Number of participants with AEs and SAEs

Timeframe: Up to 6 years

Part 1: Number of participants achieving DLTs

Timeframe: Up to 28 days

Part 1, Part 2 Dose escalation and dose expansion: Percentage of participants achieving overall response rate

Timeframe: Up to 6 years

Part 1: Progression-free survival (PFS)

Timeframe: Up to 6 years

Part 1: Overall survival

Timeframe: Up to 6 years

Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 1: Time of maximum concentration observed (Tmax) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 1: Apparent terminal phase half-life (t1/2) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

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

Timeframe: Up to 6 years

Part 1: AUC from 0 hours to the time of next dosing (AUC[0-tau]) of GSK3326595

Timeframe: Up to 6 years

Part 1: AUC(0-inf) from time zero to infinity (AUC[0-inf]) of GSK3326595

Timeframe: Up to 6 years

Part 1: Oral clearance (CL/F) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 1: Time invariance (TI) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 1: Accumulation ratio (AR) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation: Number of participants achieving CR

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: Cmax of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: Tmax of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: t1/2 of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: AUC(0-t) of GSK3326595 and 5-azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: AUC(0-inf) of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: AUC(0-tau) of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: CL/F of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: TI of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose escalation and dose expansion: AR of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration

Timeframe: Up to 6 years

Part 2 Dose expansion: Number of participants with dose interruptions, dose reductions and treatment discontinuation due to adverse events.

Timeframe: Up to 6 years

Interventions:
Drug: GSK3326595
Drug: 5-Azacitidine
Enrollment:
30
Observational study model:
Not applicable
Primary completion date:
2022-11-01
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
GSK3326595, azacitidine
Collaborators
NA
Study date(s)
October 2018 to January 2022
Type
Interventional
Phase
1/2

Participation criteria

Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
  • Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained).
  • Diagnosis of MDS, CMML or AML
  • History of, or known, central nervous system (CNS) involvement
  • Prior solid organ transplantation
Inclusion and exclusion criteria
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.

Trial location(s)

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

Study documents

Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2022-11-01
Actual study completion date
2022-11-01

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information
Not applicable
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