Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06317649 |
| Other study ID # |
NCI-2024-01987 |
| Secondary ID |
NCI-2024-01987MM |
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 3, 2025 |
| Est. completion date |
October 31, 2025 |
Study information
| Verified date |
June 2024 |
| Source |
National Cancer Institute (NCI) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 CR/complete remission with incomplete count
recovery (CRi)/complete 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 CR/CRi/CRh 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.
