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RecruitingNCT04140487

Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm

A Phase I/II Study of Azacitidine, Venetoclax, and Gilteritinib for Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome With an Activating FLT3 Mutation

Status
Recruiting
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
97 (estimated)
Sponsor
M.D. Anderson Cancer Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I/II 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 syndrome/myeloproliferative 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 syndrome/myeloproliferative neoplasm.

Detailed description

PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of the combination of azacitidine, venetoclax and gilteritinib in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML) or high-risk myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). (Phase I) II. To determine the complete remission/complete remission with incomplete count recovery (CR/CRi) rate of the regimen in patients with newly diagnosed or relapsed/refractory fms-like tyrosine kinase 3 (FLT3)-mutated AML or CMML or high-risk MDS/MPN. (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.

Conditions

Interventions

TypeNameDescription
DRUGAzacitidineGiven IV
DRUGGilteritinibGiven PO
DRUGVenetoclaxGiven PO

Timeline

Start date
2019-12-17
Primary completion
2028-09-01
Completion
2028-09-01
First posted
2019-10-28
Last updated
2026-04-16

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04140487. Inclusion in this directory is not an endorsement.