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The purpose of this study is to determine the tolerated dose of the combination of decitabine and midostaurin as induction (first cycle of chemotherapy) and consolidation (additional chemotherapy once a patient goes into remission) in people greater than 60 years with newly diagnosed AML or adult patients with relapsed/refractory disease.
The development of a primarily outpatient treatment option for AML that is also capable of providing significant disease control is a priority for most clinicians. To address the need for less toxic, more effective treatments for older patients with AML, the purpose of this Phase 1 single institution study is to evaluate the safety and efficacy of midostaurin and decitabine administered in combination.
Decitabine is an epigenetic modifier of gene expression that has been shown to be well-tolerated in this population at the dose schedule proposed in this study, with reasonable efficacy. Although its precise mechanism of action is incompletely understood, it is postulated to work by reactivating the expression of key tumor suppressor genes silenced in tumor cells by reversing a pattern of hypermethylation of promotor elements.
Midostaurin is an oral agent that has been shown to inhibit FLT3 kinase in preclinical in vitro and in vivo studies, as well as clinically in patients with both ITD and TKD FLT3 mutations (FLT3mut). Both directly and indirectly, midostaurin also potently inhibits multiple other molecular targets thought to be important for the pathogenesis of AML. These targets include VEGFR-1, a VEGF receptor; c-kit; H- and K-ras; as well as the multidrug resistant gene, MDR.
The addition of midostaurin to a decitabine regimen of previously established efficacy and tolerability will allow us to evaluate the hypothesis that two drugs that are believed to work through distinct mechanisms of action may act together to improve the responses of patients treated with decitabine alone, without significant additional toxicity.
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Acute Myeloid Leukemia
combination therapy using decitabine and midostaurin
University of Kansas Medical Center, Westwood Campus
University of Kansas
Published on BioPortfolio: 2014-07-23T21:08:58-0400
This phase II trial studies how well midostaurin and decitabine work in treating older patients with newly diagnosed acute myeloid leukemia and fms-related tyrosine kinase 3 (FLT3) mutatio...
This is an open label, single arm study of midostaurin in patients with relapsed or refractory AML.
The purpose of this study is to confirm the preliminary evidence from early clinical trials that midostaurin may provide clinical benefit not only to AML patients with the FLT3-mutations b...
This prospective multicenter clinical study was designed to assess the efficacy and safety of decitabine in combination with low-dose cytarabine induction treatment for elderly patients wi...
Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Monotherapy in Patients With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia.
The purpose of this study is to gather and evaluate additional safety and efficacy data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-l...
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A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.
A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.
An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.
An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...