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
Other
Other
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
    Primary completion date:
    2022-11-01
    Observational study model:
    Not applicable
    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
    Contact us
    Contact us
    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
    Contact us
    Location
    GSK Investigational Site
    Miami, Florida, United States, 33136
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Toronto, Ontario, Canada, M5G 2M9
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Birmingham, Alabama, United States, 35294-3300
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Milwaukee, Wisconsin, United States, 53226
    Status
    Study Complete
    Contact us
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    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
    Other
    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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