The purpose of this study is to find the appropriate dose of the study drug nintedanib when
combined with azacitidine and the associated side effects of the combination in older adults
with AML characterized by HOX gene overexpression who are not interested in or not considered
fit for standard intensive chemotherapy. The use of the study drug nintedanib in this study
is investigational. Investigational means that this medication has not yet been approved by
the FDA to treat this type of cancer. Azacitidine received FDA Approval in 2004 for
myelodysplastic syndrome (a blood cancer related to AML) and has a National Comprehensive
Cancer Network (NCCN) guideline recommendation for treatment of older adults who are not
candidates for or decline intensive remission induction therapy. We expect participation to
continue in this study based on each participant's response to the drug, and ability to
tolerate treatment. Participants may continue to receive study treatments for 6 cycles (one
cycle is 28 days long). If the 6 cycles of treatment is completed, participants may be moved
on to a maintenance phase of treatment. Treatment will continue until the participant's
leukemia gets worse, or they experience serious side effects, have a break in treatment for
more than 56 days or the study doctor feels it is best for study treatments to stop.
I. To identify maximum tolerated dose (MTD) of nintedanib for combination treatment of
nintedanib and azacytidine (5-azacitidine) in the treatment of newly diagnosed and
relapsed/refractory acute myeloid leukemia with HOX overexpression and who are ineligible for
I. Adverse events (AEs) including dose limiting toxicities (DLTs) will be assessed according
to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
II. To determine median overall survival. III. To determine complete remission (CR) rate.
I. To determine composite CR rate (CR + complete remission with incomplete platelet recovery
[CRp] + complete remission with incomplete hematological recovery [Cri]).
II. To determine duration of confirmed response. III. To determine event free survival. IV.
To determine leukemia free survival. V. To establish correlation between response and
pre-treatment Fgf2 levels and change in Fgf-2 levels during treatment.
OUTLINE: This is a dose-escalation study of azacitidine.
Participants receive nintedanib orally (PO) twice daily (BID) on days 1-28 and azacitidine
intravenously (IV) or subcutaneously (SC) on days 1-7. Treatment repeats every 28 days for up
to 6 courses in the absence of disease progression or unacceptable toxicity. After completion
of 6 courses, participants may discontinue treatment, receive nintedanib every 4-8 weeks, or
receive nintedanib and azacitidine every 4-8 weeks.
After completion of study treatment, participants are followed up at every 3 months for 12
months and then every 6 months for up to 24 months.
Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A, Fibroblast Growth Factor Basic Form Measurement, FLT3 Internal Tandem Duplication, Recurrent Adult Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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