Ignite Creation Date:
2024-05-06 @ 3:58 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02418000
Status:
TERMINATED
Last Update Posted:
2019-03-20
First Post:
2015-02-18
Brief Title:
A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 andor Ras Mutations
Sponsor:
Spirita Oncology LLC
Organization:
Spirita Oncology LLC
Study Overview
Official Title:
A Phase 12a Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 andor Ras Mutations Including Acute Myeloid Leukemia AML Myelodysplastic Syndrome MDS or Chronic Myelomonocytic Leukemia CMML
Status:
TERMINATED
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Insufficient efficacy in Phase 1 dose-escalation portion of study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase 12a dose-escalation study of E6201 a dual mitogen-activated protein kinaseextracellular-signal regulated kinase 1 MEK1 and FMS-like tyrosine kinase 3 FLT3 inhibitor in subjects with advanced hematologic malignancies with documented FLT3 andor rat sarcoma Ras mutations The Phase1 portion of the study will be a safety run-in up to 30 subjects to establish a recommended Phase 2 dose RP2D The Ph 2a portion of the study will evaluate three specific patients groups Cohort 1 will enroll patients with relapsed or refractory AML and confirmed FLT3 mutation with or without a Ras mutation without prior exposure to a FLT3 inhibitor Cohort 2 will enroll patients with relapsed or refractory AML and confirmed FLT3 mutation with or without a Ras mutation with prior exposure to a FLT3 inhibitor Cohort 3 will enroll patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation
Detailed Description:
Phase 1 Safety Run-In Following Screening a total of up to 30 subjects in up to 5 dose cohorts to establish the RP2D The safety run-in phase will be a standard 33 cohort design
Phase 2a Expansion Once the Phase 1 Safety Run-In portion of the study is complete and an RP2D is established additional subjects will be enrolled into the Phase 2 Expansion portion in three cohorts Cohort 1 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation with or without a Ras mutation without prior exposure to a FLT3 inhibitor Cohort 2 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation with or without a Ras mutation with prior exposure to a FLT3 inhibitor Cohort 3 will enroll up to 10 patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation Cohort 1 and 2 of the Expansion Phase will incorporate a Simon 2-stage optimal design Subjects with AML enrolled in the Phase 1 portion of the study at the RP2D will count towards the Phase 2a accrual for the appropriate cohort
Subjects will receive E6201 weekly or bi-weekly on a 28-day schedule with the schedule and dose level established in the Safety Run-In portion of the study Disease assessments including analysis of blood and bone marrow samples will be performed at the end of Cycles 1 and 3 and every 2 cycles thereafter Disease assessments may be made at other time points at the discretion of the Investigator
Subjects who demonstrate clinical benefit objective response or stable disease will be allowed to continue therapy with E6201 until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the patients condition that prevents further study participation
During the study ECGs will be performed blood will be collected for hematology serum chemistry pharmacokinetics and pharmacodynamics assessments and bone marrow will be collected for the assessment of disease response and mutational status
Phase 2a Expansion Once the Phase 1 Safety Run-In portion of the study is complete and an RP2D is established additional subjects will be enrolled into the Phase 2 Expansion portion in three cohorts Cohort 1 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation with or without a Ras mutation without prior exposure to a FLT3 inhibitor Cohort 2 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation with or without a Ras mutation with prior exposure to a FLT3 inhibitor Cohort 3 will enroll up to 10 patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation Cohort 1 and 2 of the Expansion Phase will incorporate a Simon 2-stage optimal design Subjects with AML enrolled in the Phase 1 portion of the study at the RP2D will count towards the Phase 2a accrual for the appropriate cohort
Subjects will receive E6201 weekly or bi-weekly on a 28-day schedule with the schedule and dose level established in the Safety Run-In portion of the study Disease assessments including analysis of blood and bone marrow samples will be performed at the end of Cycles 1 and 3 and every 2 cycles thereafter Disease assessments may be made at other time points at the discretion of the Investigator
Subjects who demonstrate clinical benefit objective response or stable disease will be allowed to continue therapy with E6201 until progression of disease observation of unacceptable adverse events intercurrent illness or changes in the patients condition that prevents further study participation
During the study ECGs will be performed blood will be collected for hematology serum chemistry pharmacokinetics and pharmacodynamics assessments and bone marrow will be collected for the assessment of disease response and mutational status
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None