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.
Title
- Brief Title: Study to Investigate the Safety and Clinical Activity of GSK3326595 and Other Agents to Treat Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
- 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
Clinical Trial IDs
- ORG STUDY ID:
208809
- NCT ID:
NCT03614728
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| GSK3326595 | | Part 1: Participants receiving GSK3326595 |
| 5-Azacitidine | | Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine |
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1: Participants receiving GSK3326595 | Experimental | | |
| Part 2 Dose escalation : Participants receiving GSK3326595+5-Azacitidine | Experimental | | |
| Part 2 Dose expansion: Participants receiving GSK3326595+5-Azacitidine | Experimental | | |
Eligibility 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1: Percentage of participants with clinical benefit rate (CBR) |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Part 1 and Part 2 Dose expansion: Number of participants with AEs and SAEs |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | All AEs and SAEs will be collected. |
| Measure: | Part 1: Number of participants achieving DLTs |
| Time Frame: | Up to 28 days |
| Safety Issue: | |
| Description: | An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets the Non-hematologic toxicity, hematologic toxicity and other toxicity criteria unless it can be clearly established that the event is unrelated to treatment. |
| Measure: | Part 1, Part 2 Dose escalation and dose expansion: Percentage of participants achieving overall response rate |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Overall response rate is defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria. |
| Measure: | Part 1: Progression-free survival (PFS) |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | PFS is defined as time from first dose to disease progression, as defined by IWG criteria, or death due to any cause, whichever occurs first. |
| Measure: | Part 1: Overall survival |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Overall survival is defined time from first dose to death due to any cause. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine Cmax of GSK3326595. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine Tmax of GSK3326595. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine t1/2 of GSK3326595. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AUC(0-t) of GSK3326595. |
| Measure: | Part 1: AUC from 0 hours to the time of next dosing (AUC[0-tau]) of GSK3326595 |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AUC(0-tau) of GSK3326595. |
| Measure: | Part 1: AUC(0-inf) from time zero to infinity (AUC[0-inf]) of GSK3326595 |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AUC(0-inf) of GSK3326595. |
| Measure: | Part 1: Oral clearance (CL/F) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine CL/F of GSK3326595. |
| Measure: | Part 1: Time invariance (TI) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine TI of GSK3326595. |
| Measure: | Part 1: Accumulation ratio (AR) of GSK3326595 in plasma following single- (Day 1) and repeat-dose administration |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AR of GSK3326595. |
| Measure: | Part 2 Dose escalation: Number of participants achieving CR |
| Time Frame: | Up to 6 years |
| Safety Issue: | |
| Description: | CR rate is defined as the percentage of participants achieving a CR per IWG criteria. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine Cmax of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine Tmax of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine t1/2 of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AUC(0-t) of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AUC(0-inf) of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AUC(0-tau) of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine CL/F of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine TI of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected to determine AR of GSK3326595 and 5-Azacitidine. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Participants with dose interruptions, dose reductions and treatment discontinuation due to adverse events will be assessed. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | GlaxoSmithKline |
Trial Keywords
- Acute myeloid leukemia
- Myelodysplastic syndrome
- Chronic myelomonocytic leukemia
- GSK3326595
- 5-Azacitidine
Last Updated
August 26, 2021
