Clinical Trial - NCT03614728

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

Recruiting

Sponsor: GlaxoSmithKline

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03614728

Protocol Info

Short Description: GSK3326595 in Acute Myeloid Leukaemia + Myelodysplastic
Long Description: A Phase I/II study to investigate the safety and clinical activity of GSK3326595 and other agents in subjects with myelodysplastic syndrome and acute myeloid leukaemia
MGH Status: Open
Sponsor: GlaxoSmithKline
Disease Program: Leukemia

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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.
Condition Title Intervention Phase
Neoplasms GSK3326595 5-Azacitidine Phase 1
Study Type Interventional
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

Primary Outcome Measures

Part 1: Percentage of participants with clinical benefit rate (CBR) [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation: Number of participants with adverse events and serious adverse events (AEs and SAEs) [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation: Number of participants achieving dose limiting toxicities (DLTs) [Time Frame: Up to 28 days] [Designated as safety issue: ]

Part 2 Dose escalation: Number of participants with dose interruptions, dose reductions and treatment discontinuation due to adverse events. [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose expansion: Number of participants achieving CR [Time Frame: Up to 6 years] [Designated as safety issue: ]


Secondary Outcome Measures

Part 1 and Part 2 Dose expansion: Number of participants with AEs and SAEs [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Number of participants achieving DLTs [Time Frame: Up to 28 days] [Designated as safety issue: ]

Part 1, Part 2 Dose escalation and dose expansion: Percentage of participants achieving overall response rate [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Progression-free survival (PFS) [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Overall survival [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Time of maximum concentration observed (Tmax) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Apparent terminal phase half-life (t1/2) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

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 [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: AUC from 0 hours to the time of next dosing (AUC[0-tau]) of GSK3326595 [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: AUC(0-inf) from time zero to infinity (AUC[0-inf]) of GSK3326595 [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Oral clearance (CL/F) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Time invariance (TI) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 1: Accumulation ratio (AR) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation: Number of participants achieving CR [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation and dose expansion: Cmax of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation and dose expansion: Tmax of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation and dose expansion: t1/2 of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

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 [Time Frame: Up to 6 years] [Designated as safety issue: ]

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 [Time Frame: Up to 6 years] [Designated as safety issue: ]

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 [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation and dose expansion: CL/F of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation and dose expansion: TI of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose escalation and dose expansion: AR of GSK3326595 and 5-Azacitidine in plasma following single- (Day 1) and repeat-dose administration [Time Frame: Up to 6 years] [Designated as safety issue: ]

Part 2 Dose expansion: Number of participants with dose interruptions, dose reductions and treatment discontinuation due to adverse events. [Time Frame: Up to 6 years] [Designated as safety issue: ]

Estimated Enrollment: 113
Study Start Date: October 2018
Estimated Study Completion Date: April 2025
Estimated Primary Completion Date: April 2025
Arms Assigned Interventions

Experimental:Part 1: Participants receiving GSK3326595

Drug:GSK3326595
GSK3326595 will be administered.

Experimental:Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine

Drug:5-Azacitidine
5-Azacitidine will be administered.

Experimental:Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03614728

Locations

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

Sponsors and Collaborators

GlaxoSmithKline

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03614728
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by GlaxoSmithKline:

Acute myeloid leukemia

Myelodysplastic syndrome

Chronic myelomonocytic leukemia

GSK3326595

5-Azacitidine

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Azacitidine

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on April 29, 2021