Ignite Creation Date:
2024-05-06 @ 8:15 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06317649
Status:
RECRUITING
Last Update Posted:
2024-07-11
First Post:
2024-03-16
Brief Title:
Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia AML A MyeloMATCH Treatment Trial
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase II Study of Venetoclax and HMA-Based Therapies for the Treatment of Older and Unfit Adults With Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia AML A MyeloMATCH Treatment Trial
Status:
RECRUITING
Status Verified Date:
2024-09
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 II MyeloMATCH treatment trial compares the usual treatment of azacitidine and venetoclax to the combination treatment of azacitidine venetoclax and gilteritinib in treating older and unfit patients with acute myeloid leukemia and FLT3 mutations Azacitidine is a drug that is absorbed into DNA and leads to the activation of cancer suppressor genes which are genes that help control cell growth Venetoclax is in a class of medications called B-cell lymphoma-2 BCL-2 inhibitors It may stop the growth of cancer cells by blocking Bcl-2 a protein needed for cancer cell survival Gilteritinib is in a class of medications called kinase inhibitors It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply This study may help doctors find out if these different approaches are better than the usual approaches To decide if they are better the study doctors are looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to the usual approach
Detailed Description:
PRIMARY OBJECTIVE
I To compare the achievement rate of measured residual disease negative MRDneg complete remission CR of either triplet regimen to azacitidine and venetoclax alone within 4 cycles of therapy
SECONDARY OBJECTIVES
I To compare the achievement rate of MRDneg CRcomplete remission with incomplete count recovery CRicomplete remission with partial hematologic recovery CRh of either triplet regimen to azacitidine and venetoclax alone within 4 cycles of therapy
II To determine the safety and tolerability of the combination of gilteritinib azacitidine and venetoclax if both of the triplet regimens show superiority to the azacitidine plus venetoclax regimen
III To determine the optimal sequence and duration of gilteritinib when added to azacitidine and venetoclax if both of the triplet regimens show superiority to the azacitidine plus venetoclax regimen
IV To estimate the rates of complete remission CR complete remission with incomplete count recovery CRi and complete remission with partial hematologic recovery CRh morphologic leukemia-free state MLFS event-free survival EFS and overall survival OS of the combination of gilteritinib azacitidine and venetoclax versus azacitidine and venetoclax alone
EXPLORATORY OBJECTIVES
I To establish the degree reduction in FLT3- internal tandem duplication ITD mutation burden after 2 and 4 cycles of therapy using a highly sensitive next-generation sequencing NGS MRD assay and compare the median reduction in the investigational regimens among patients with CRCRiCRh to that of control regimen
II To determine if the degree of FLT3 ITD reduction is associated with the duration of remission
III To monitor which mutations are present at the time of relapse IV To monitor which co-mutations at presentation are associated with lack of response to these regimens
V To determine if the FLT3 AR variant allele frequency VAF is associated with response to the regimens
OUTLINE Patients are randomized to 1 of 3 regimens
REGIMEN 1
INDUCTION Patients receive azacitidine intravenously IV or subcutaneously SC on days 1-7 of each cycle and venetoclax orally PO on days 1-28 of each cycle Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission whichever comes first in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 of each cycle Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
REGIMEN 2
INDUCTION Patients receive azacitidine IV or SC on days 1-7 and venetoclax and gilteritinib PO on days 1-28 of each cycle Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission whichever comes first in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive azacitidine IV or SC on days 1-5 venetoclax PO on days 1-7 and gilteritinib PO on days 1-28 of each cycle Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
REGIMEN 3
INDUCTION Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 and gilteritinib PO on days 8-21 of each cycle Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission whichever comes first in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive azacitidine IV or SC on days 1-5 venetoclax PO on days 1-14 and gilteritinib PO on days 8-21 of each cycle Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
All patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial
After completion of study treatment patients are followed up every 3 months if patient is 2 years from first registration and every 6 months if patient is 2-5 years from first registration All patients including those who discontinue protocol therapy early are followed for response until progression even if non-protocol therapy is initiated and for survival for 10 years from the date of randomization
I To compare the achievement rate of measured residual disease negative MRDneg complete remission CR of either triplet regimen to azacitidine and venetoclax alone within 4 cycles of therapy
SECONDARY OBJECTIVES
I To compare the achievement rate of MRDneg CRcomplete remission with incomplete count recovery CRicomplete remission with partial hematologic recovery CRh of either triplet regimen to azacitidine and venetoclax alone within 4 cycles of therapy
II To determine the safety and tolerability of the combination of gilteritinib azacitidine and venetoclax if both of the triplet regimens show superiority to the azacitidine plus venetoclax regimen
III To determine the optimal sequence and duration of gilteritinib when added to azacitidine and venetoclax if both of the triplet regimens show superiority to the azacitidine plus venetoclax regimen
IV To estimate the rates of complete remission CR complete remission with incomplete count recovery CRi and complete remission with partial hematologic recovery CRh morphologic leukemia-free state MLFS event-free survival EFS and overall survival OS of the combination of gilteritinib azacitidine and venetoclax versus azacitidine and venetoclax alone
EXPLORATORY OBJECTIVES
I To establish the degree reduction in FLT3- internal tandem duplication ITD mutation burden after 2 and 4 cycles of therapy using a highly sensitive next-generation sequencing NGS MRD assay and compare the median reduction in the investigational regimens among patients with CRCRiCRh to that of control regimen
II To determine if the degree of FLT3 ITD reduction is associated with the duration of remission
III To monitor which mutations are present at the time of relapse IV To monitor which co-mutations at presentation are associated with lack of response to these regimens
V To determine if the FLT3 AR variant allele frequency VAF is associated with response to the regimens
OUTLINE Patients are randomized to 1 of 3 regimens
REGIMEN 1
INDUCTION Patients receive azacitidine intravenously IV or subcutaneously SC on days 1-7 of each cycle and venetoclax orally PO on days 1-28 of each cycle Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission whichever comes first in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 of each cycle Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
REGIMEN 2
INDUCTION Patients receive azacitidine IV or SC on days 1-7 and venetoclax and gilteritinib PO on days 1-28 of each cycle Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission whichever comes first in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive azacitidine IV or SC on days 1-5 venetoclax PO on days 1-7 and gilteritinib PO on days 1-28 of each cycle Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
REGIMEN 3
INDUCTION Patients receive azacitidine IV or SC on days 1-7 and venetoclax PO on days 1-28 and gilteritinib PO on days 8-21 of each cycle Treatment repeats every 28 days for up to 2 cycles or until patient achieves remission whichever comes first in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive azacitidine IV or SC on days 1-5 venetoclax PO on days 1-14 and gilteritinib PO on days 8-21 of each cycle Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
All patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial
After completion of study treatment patients are followed up every 3 months if patient is 2 years from first registration and every 6 months if patient is 2-5 years from first registration All patients including those who discontinue protocol therapy early are followed for response until progression even if non-protocol therapy is initiated and for survival for 10 years from the date of randomization
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 |
|---|---|---|---|
| U10CA180820 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180820 |
| NCI-2024-01987 | REGISTRY | None | None |
| MM1OA-EA02 | OTHER | None | None |
| MM1OA-EA02 | OTHER | None | None |