A Phase 2 interventional study of Azacitidine and Biospecimen Collection in Acute Myeloid Leukemia, sponsored by National Cancer Institute (NCI). Recruiting at 227 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-07.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
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 of 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 leukemia-associated 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 variant allele frequency (VAF) at study enrollment 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 bone marrow assessment shows at least an MLFS response or better ("better" defined as CR, CRi, CRh), 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 bone marrow assessment shows at least an MLFS response or better ("better" defined as CR, CRi, CRh), 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 bone marrow assessment shows at least an MLFS response or better ("better" defined as CR, CRi, CRh), 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 randomization, every 6 months if patient is 2-5 years from randomization, and every year if patient is 5-10 years from randomization. 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.
2,970 studies on the registry are indexed under Leukemia, Myeloid, Acute; 744 are open to participants now.
This study's planned enrollment of 147 is above the median of 41 across 2,508 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Creatinine clearance ≥ 30 mL/min (must be obtained ≤ 14 days prior to randomization)
Patients who meet the criteria below must have had an electrocardiogram (ECG) performed with a corrected QT interval using Fridericia's correction (QTcF) interval within normal limits:
Risk for electrolyte abnormalities, including tumor lysis syndrome
INDUCTION: Patients receive azacitidine IV or SC on days 1-7 of each cycle and venetoclax PO on days 1-28 of each cycle. Treatment repeats every 28 days for up to 2 cycles or until bone marrow assessment shows at least an MLFS response or better ("better" defined as CR, CRi, CRh), 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. Patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.
Drug: Azacitidine · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Venetoclax
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 bone marrow assessment shows at least an MLFS response or better ("better" defined as CR, CRi, CRh), 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. Patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.
Drug: Azacitidine · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Gilteritinib · Drug: Venetoclax
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 bone marrow assessment shows at least an MLFS response or better ("better" defined as CR, CRi, CRh), 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. Patients undergo bone marrow biopsy and aspiration as well as blood sample collection on the trial.
Drug: Azacitidine · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Gilteritinib · Drug: Venetoclax
Given IV or SC
Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo bone marrow biopsy and aspiration
Undergo bone marrow biopsy and aspiration
Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Given PO
Also known as: ASP 2215, ASP-2215, ASP2215
Given PO
Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto
Rate of measured residual disease (MRD) negative complete remission (CR)
Will be assessed by multiparameter flow cytometry at a level of ≤ 1 residual blast / 1,000 leukocytes (≤ 10\^-3). Patients achieved MRD negative CR at any time up to 4 cycles will count as a responder. The MRD negative CR frequencies will be compared between each triplet regimen and the control regimen using Fisher's exact test with one-sided alpha of 0.05 for each comparison. Test results with one-sided p-value \< 0.05 will be considered statistically significant.
Time frame: Up to 4 cycles of treatment (1 cycle = 28 days)
Rate of MRD negative CR/CR with incomplete count recovery (CRi)/CR with partial hematologic recovery (CRh)
Patients who achieved MRD negative CR at any time up to 4 cycles will count as a responder. The MRD negative CR frequencies will be compared between each triplet regimen and the control regimen using Fisher's exact test with one-sided alpha of 0.05 for each comparison. Test results with one-sided p-value \< 0.05 will be considered statistically significant.
Time frame: Up to 4 cycles of treatment (1 cycle = 28 days)
Rate of CR
The CR rates will be compared using Fisher's exact test. Only nominal p-values will be provided.
Time frame: Up to 10 years
Rate of CRi
The CR rates will be compared using Fisher's exact test. Only nominal p-values will be provided.
Time frame: Up to 10 years
Rate of CRh
The CR rates will be compared using Fisher's exact test. Only nominal p-values will be provided.
Time frame: Up to 10 years
Overall survival
Will be calculated using the Kaplan-Meier method.
Time frame: Time between randomization and death from any cause, assessed up to 10 years
Event-free survival
Will be calculated using the Kaplan-Meier method.
Time frame: Time from randomization to failure to achieve CR, CRi, and CRh, or to relapse after CR/CRi/CRh or to death in remission, assessed up to 10 years
Incidence of adverse events
Will be determined using the Common Terminology Criteria for Adverse Events.
Time frame: Up to 10 years
Showing the first 100 of 227 sites across 2 countries.
Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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