Ignite Creation Date:
2024-05-06 @ 1:52 PM
Last Modification Date:
2024-10-26 @ 1:21 PM
Study NCT ID:
NCT04140487
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2019-08-19
Brief Title:
Azacitidine Venetoclax and Gilteritinib in Treating Patients With RecurrentRefractory FLT3-Mutated Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia or High-Risk Myelodysplastic SyndromeMyeloproliferative Neoplasm
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
A Phase III Study of Azacitidine Venetoclax and Gilteritinib for Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome With an Activating FLT3 Mutation
Status:
RECRUITING
Status Verified Date:
2024-10
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 side effects and best dose of gilteritinib and to see how well it works in combination with azacitidine and venetoclax in treating patients with FLT3-mutation positive acute myeloid leukemia chronic myelomonocytic leukemia or high-risk myelodysplastic syndromemyeloproliferative neoplasm that has come back recurrent or has not responded to treatment refractory Drugs used in chemotherapy such as azacitidine 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 azacitidine venetoclax and gilteritinib may work better compared to azacitidine and venetoclax alone in treating patients with acute myeloid leukemia chronic myelomonocytic leukemia or myelodysplastic syndromemyeloproliferative neoplasm
Detailed Description:
PRIMARY OBJECTIVES
I To establish the maximum tolerated dose MTD of the combination of azacitidine venetoclax and gilteritinib in patients with relapsedrefractory FLT3-mutated acute myeloid leukemia AML or chronic myelomonocytic leukemia CMML or high-risk myelodysplastic syndromemyeloproliferative neoplasm MDSMPN Phase I II To determine the complete remissioncomplete remission with incomplete count recovery CRCRi rate of the regimen in patients with newly diagnosed or relapsedrefractory fms-like tyrosine kinase 3 FLT3-mutated AML or CMML or high-risk MDSMPN 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
OUTLINE This is phase I dose-escalation study of gilteritinib followed by a phase II study
Patients receive azacitidine subcutaneously SC or intravenously IV over 30-60 minutes on days 1-7 venetoclax orally PO once daily QD on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles and gilteritinib PO QD on days 1-28 Treatment of azacytidine and venetoclax repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity Cycles of gilteritinib 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 and then every 6 months thereafter
I To establish the maximum tolerated dose MTD of the combination of azacitidine venetoclax and gilteritinib in patients with relapsedrefractory FLT3-mutated acute myeloid leukemia AML or chronic myelomonocytic leukemia CMML or high-risk myelodysplastic syndromemyeloproliferative neoplasm MDSMPN Phase I II To determine the complete remissioncomplete remission with incomplete count recovery CRCRi rate of the regimen in patients with newly diagnosed or relapsedrefractory fms-like tyrosine kinase 3 FLT3-mutated AML or CMML or high-risk MDSMPN 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
OUTLINE This is phase I dose-escalation study of gilteritinib followed by a phase II study
Patients receive azacitidine subcutaneously SC or intravenously IV over 30-60 minutes on days 1-7 venetoclax orally PO once daily QD on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles and gilteritinib PO QD on days 1-28 Treatment of azacytidine and venetoclax repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity Cycles of gilteritinib 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 and 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 |
|---|---|---|---|
| 2019-0366 | OTHER | M D Anderson Cancer Center | None |
| NCI-2019-04959 | REGISTRY | None | None |