Ignite Creation Date:
2024-05-06 @ 4:31 PM
Last Modification Date:
2024-10-26 @ 2:11 PM
Study NCT ID:
NCT05010122
Status:
RECRUITING
Last Update Posted:
2024-06-11
First Post:
2021-07-22
Brief Title:
ASTX727 Venetoclax and Gilteritinib for the Treatment of Newly Diagnosed Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
A Phase III Study of ASTX727 Venetoclax and Gilteritinib for Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome With an Activating FLT3 Mutation
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies the best dose of gilteritinib given together with ASTX727 and venetoclax and the effect of ASTX727 venetoclax and gilteritinib in treating patients with FLT3-mutated acute myeloid leukemia that is newly diagnosed has come back relapsed or does not respond to treatment refractory or high-risk myelodysplastic syndrome Chemotherapy drugs such as ASTX727 work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading Venetoclax may stop the growth of cancer cells by blocking Bcl-2 a protein needed for cancer cell survival Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Giving ASTX727 venetoclax and gilteritinib may help to control the disease
Detailed Description:
PRIMARY OBJECTIVES
I To establish the maximum tolerated dose MTD of the combination of decitabine and cedazuridine ASTX727 venetoclax and gilteritinib in patients with relapsedrefractory FLT3- mutated acute myeloid leukemia AML or high-risk myelodysplastic syndrome MDS Phase I II To determine the complete response CRincomplete hematologic recovery CRi rate of the regimen in patients with newly diagnosed or relapsedrefractory FLT3-mutated AML or high-risk MDS Phase II
SECONDARY OBJECTIVES
I To assess other efficacy endpoints CR rate minimal residual disease negativity by flow cytometry relapse-free survival overall survival
II To assess proportion of patients proceeding to hematopoietic stem cell transplantation HSCT
III To determine the safety of the combination regimen
EXPLORATORY OBJECTIVES
I To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen
II To determine the impact of baseline FLT3 allelic ratio on response and survival
III To evaluate clonal evolution from diagnosis to relapse using single-cell sequencing
IV To evaluate potential role of minimal residual disease MRD detection by sensitive polymerase chain reaction PCRnext generation sequencing NGS assays for FLT3 mutations
V To evaluate leukemia stem cell populations over the course of treatment with the combination regimen
VI To determine the impact of baseline apoptotic protein levels as assessed by mass cytometry CyTOF on response and resistance to the regimen
OUTLINE This is a phase I dose-escalation study of gilteritinib followed by a phase II study
INDUCTION CYCLE 1 Patients receive decitabine and cedazuridine orally PO once daily QD on days 1-5 venetoclax PO QD on days 1-28 and gilteritinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity
CONSOLIDATION CYCLES 2-24 Patients receive decitabine and cedazuridine PO QD on days 1-5 gilteritinib PO QD on days 1-28 and venetoclax PO QD on days 1-21 Treatment repeats every 28 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE CYCLES 24 Patients receive gilteritinib PO QD on days 1-28 Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days then every 6 months thereafter
I To establish the maximum tolerated dose MTD of the combination of decitabine and cedazuridine ASTX727 venetoclax and gilteritinib in patients with relapsedrefractory FLT3- mutated acute myeloid leukemia AML or high-risk myelodysplastic syndrome MDS Phase I II To determine the complete response CRincomplete hematologic recovery CRi rate of the regimen in patients with newly diagnosed or relapsedrefractory FLT3-mutated AML or high-risk MDS Phase II
SECONDARY OBJECTIVES
I To assess other efficacy endpoints CR rate minimal residual disease negativity by flow cytometry relapse-free survival overall survival
II To assess proportion of patients proceeding to hematopoietic stem cell transplantation HSCT
III To determine the safety of the combination regimen
EXPLORATORY OBJECTIVES
I To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen
II To determine the impact of baseline FLT3 allelic ratio on response and survival
III To evaluate clonal evolution from diagnosis to relapse using single-cell sequencing
IV To evaluate potential role of minimal residual disease MRD detection by sensitive polymerase chain reaction PCRnext generation sequencing NGS assays for FLT3 mutations
V To evaluate leukemia stem cell populations over the course of treatment with the combination regimen
VI To determine the impact of baseline apoptotic protein levels as assessed by mass cytometry CyTOF on response and resistance to the regimen
OUTLINE This is a phase I dose-escalation study of gilteritinib followed by a phase II study
INDUCTION CYCLE 1 Patients receive decitabine and cedazuridine orally PO once daily QD on days 1-5 venetoclax PO QD on days 1-28 and gilteritinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity
CONSOLIDATION CYCLES 2-24 Patients receive decitabine and cedazuridine PO QD on days 1-5 gilteritinib PO QD on days 1-28 and venetoclax PO QD on days 1-21 Treatment repeats every 28 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity
MAINTENANCE CYCLES 24 Patients receive gilteritinib PO QD on days 1-28 Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days then every 6 months thereafter
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2021-0082 | OTHER | M D Anderson Cancer Center | None |
| NCI-2021-06095 | REGISTRY | None | None |