NCT01130662

Combination of Decitabine and Midostaurin in Patients Older Than 60 With Newly Diagnosed or Relapsed Refractory Acute Myeloid Leukemia

Phase I Open-Label Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly (Age ≥ 60) Newly Diagnosed or Relapsed/Refractory Adult Patients With Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of Kansas · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	combination therapy using decitabine and midostaurin	Cohort 1: Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 25mg bid days 8-21 of each cycle. Cohort 2: Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 50mg bid days 8-21 of each cycle. Cohort 3: Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 50mg bid x 28 days of each cycle.

Timeline

• Start date: 2010-03-01
• Primary completion: 2011-10-01
• Completion: 2011-10-01
• First posted: 2010-05-26
• Last updated: 2013-03-26

Locations

1 site across 1 country: United States