NCT01093573

Midostaurin and Azacitidine in Treating Elderly Patients With Acute Myelogenous Leukemia

A Phase I/II Study of Midostaurin (PKC412) and 5-Azacitidine for Elderly Patients With Acute Myelogenous Leukemia.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Brenda Cooper, MD · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

RATIONALE: Midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Midostaurin may help azacitidine kill more cancer cells by making the cancer cells more sensitive to the drug. PURPOSE: This phase I/II trial is studying the side effects and best dose of midostaurin when given together with azacitidine and to see how well it works in treating elderly patients with acute myelogenous leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safe and tolerable dose of midostaurin in combination with azacitidine in patients with acute myelogenous leukemia. (Phase I) II. To describe the toxicity profile of the combination of midostaurin and azacitidine in patients with acute myelogenous leukemia. (Phase I/II) III. To determine the complete and partial response rate and rate of hematologic improvement of midostaurin and 5-azacitidine in untreated acute myelogenous leukemia. (Phase I/II) SECONDARY OBJECTIVES: I. To describe pharmacokinetics of oral midostaurin given in combination with azacitidine on a day 8-21 schedule. (Phase I/II) II. To correlate treatment response with FLT3 mutational status in a descriptive fashion. (Phase I/II) III. To assess overall survival of patients from initiation of midostaurin-azacitidine toxicities. (Phase I/II) IV. To determine median disease-free survival of the regimen in untreated patients. (Phase II) TERTIARY OBJECTIVES: I. To describe signaling in CD117+ committed myeloid precursors in whole blood and bone marrow samples before and during treatment. (Phase I/II) II. To measure in vivo FLT3 inhibition using plasma inhibition assay (PIA) and Flt ligand (FL) levels in patients enrolled on this trial before and during treatment. (Phase I/II) OUTLINE: This is a phase I, dose escalation study of midostaurin followed by a phase II study. Patients receive azacitidine intravenously (IV) over 10-20 minutes on days 1-7 and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Conditions

• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	midostaurin	Given orally
DRUG	azacitidine	Given IV
OTHER	bone marrow aspiration	Correlative study: Pretreatment bone marrow aspirates or blood \[(3 ml in EDTA tube (purple top)\] will be analyzed according to local institution guidelines to determine whether blasts contain wild type Flt3, ITD, or Flt 3 mutations.
OTHER	mutation analysis	Correlative study
OTHER	Pharmacokinetic study	Correlative study: Concentrations of unchanged midostaurin and its major metabolites, CGP52421 and CGP62221 in plasma samples will be determined using a validated liquid chromatography / mass spectrometry method.

Timeline

• Start date: 2009-07-01
• Primary completion: 2016-09-08
• Completion: 2017-05-05
• First posted: 2010-03-26
• Last updated: 2022-06-30
• Results posted: 2020-05-01

Locations

2 sites across 1 country: United States