Ignite Creation Date:
2024-05-06 @ 5:49 PM
Last Modification Date:
2024-10-26 @ 2:36 PM
Study NCT ID:
NCT05441514
Status:
RECRUITING
Last Update Posted:
2023-12-18
First Post:
2022-06-28
Brief Title:
Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Sponsor:
City of Hope Medical Center
Organization:
City of Hope Medical Center
Study Overview
Official Title:
Phase 1b Study of IDH Inhibition With Enasidenib and MEK Inhibition With Cobimetinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Have Co-Occurring IDH2 and RAS Signaling Gene Mutations
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial tests the safety side effects and best dose of a enasidenib in combination with cobimetinib in treating patients with acute myeloid leukemia that has come back relapsed or does not respond to treatment refractory Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Cobimetinib is used in patients whose cancer has a mutated changed form of a gene called BRAF It is in a class of medications called kinase inhibitors It works by blocking the action of an abnormal protein that signals cancer cells to multiply This helps slow or stop the spread of cancer cells Giving enasidenib and cobimetinib may kill more cancer cells in patients with relapsed or refractory acute myeloid leukemia
Detailed Description:
PRIMARY OBJECTIVES
I Assess the safety and tolerability of cobimetinib in combination with enasidenib
II Determine the maximum tolerated doses MTD and recommended phase 2 dose RP2D
SECONDARY OBJECTIVES
I Obtain preliminary estimates of clinical activity as measured by the complete remission complete response CR complete response with incomplete hematologic recovery CRi or complete response with partial hematologic recovery CRh rate and minimal residual disease MRD rate
II Obtain preliminary estimates of clinical activity as measured by overall response rate CR CRi CRh morphologic leukemia free state MLFS and partial response PR
III Obtain preliminary estimates of median time to complete remission IV Obtain preliminary estimates of median time to first response V Obtain preliminary estimates of response duration in all participants and in those attaining CRCRiCRh
VI Obtain preliminary estimates of median and 1-year event-free survival EFS
VII Obtain preliminary estimates of median and 1-year overall survival OS
EXPLORATORY OBJECTIVES
I Characterize the effects of the combination on cellular differentiation of leukemic cells as measured by flow cytometry performed at study entry and at serial timepoints throughout the study
II Evaluate changes in promotor methylation patterns after treatment with combination therapy
III Evaluate changes in gene expression of RAS pathway regulators as a result of the combination therapy
OUTLINE This is dose-escalation study of cobimetinib followed by a dose-expansion study
Patients receive cobimetinib orally PO once daily QD on days 1-21 and enasidenib mesylate PO QD on days 1-28 of each cycle Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and every 3 months for 1 year at last treatment dose
I Assess the safety and tolerability of cobimetinib in combination with enasidenib
II Determine the maximum tolerated doses MTD and recommended phase 2 dose RP2D
SECONDARY OBJECTIVES
I Obtain preliminary estimates of clinical activity as measured by the complete remission complete response CR complete response with incomplete hematologic recovery CRi or complete response with partial hematologic recovery CRh rate and minimal residual disease MRD rate
II Obtain preliminary estimates of clinical activity as measured by overall response rate CR CRi CRh morphologic leukemia free state MLFS and partial response PR
III Obtain preliminary estimates of median time to complete remission IV Obtain preliminary estimates of median time to first response V Obtain preliminary estimates of response duration in all participants and in those attaining CRCRiCRh
VI Obtain preliminary estimates of median and 1-year event-free survival EFS
VII Obtain preliminary estimates of median and 1-year overall survival OS
EXPLORATORY OBJECTIVES
I Characterize the effects of the combination on cellular differentiation of leukemic cells as measured by flow cytometry performed at study entry and at serial timepoints throughout the study
II Evaluate changes in promotor methylation patterns after treatment with combination therapy
III Evaluate changes in gene expression of RAS pathway regulators as a result of the combination therapy
OUTLINE This is dose-escalation study of cobimetinib followed by a dose-expansion study
Patients receive cobimetinib orally PO once daily QD on days 1-21 and enasidenib mesylate PO QD on days 1-28 of each cycle Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and every 3 months for 1 year at last treatment dose
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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2022-04926 | REGISTRY | None | None |
| 21751 | OTHER | None | None |
| P30CA033572 | NIH | City of Hope Medical Center | httpsreporternihgovquickSearchP30CA033572 |