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

• Status: Completed
• Trial end date: 2011-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Kansas
• Collaborator: Novartis
• Treatments: 4'-N-benzoylstaurosporine; Azacitidine; Decitabine; Midostaurin; Staurosporine

Criteria

Inclusion Criteria:

• ≥ 60 years of age with newly diagnosed AML that is not eligible for standard induction or ≥ 18 years of age with relapsed/refractory AML

• Histologically documented AML (except t(15;17)according to the World Health Association (WHO) criteria

• Karnofsky performance status ≥ 70

• Must have the following lab values:

• AST and ALT < or equal to 2.5 x Upper Limit of Normal (ULN)

• Serum Bilirubin < or equal to 2.5 x ULN

• Serum Creatinine < or equal to 2.5 x ULN

• Must give written informed consent

• Left ventricular ejection fraction ≥ 50%

Exclusion Criteria:

• Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously

• Uncontrolled active infection

• Known impairment of GI function or GI disease that may significantly alter the absorption of midostaurin

• Female patients who are pregnant or breast-feeding or adults of reproductive potential not using an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of midostaurin. Women considered not of childbearing potential include any of the following: no menses for at least 5 years or menses within 5 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months.

• Other known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled medical condition (eg uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and poorly controlled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study.

• Impaired cardiac function including any of the following:

• Screening ECG with a QTc > 450 msec

• Congenital long QT syndrome

• History or presence of sustained ventricular tachycardia

• Any history of ventricular fibrillation or torsades de pointes

• Bradycardia defined as HR less than 50 bpm

• Right bundle branch block + left anterior hemiblock (bifascicular block)

• Myocardial infarction or unstable angina < 6 months prior to starting study drug

• CHF NY Heart Association class III or IV

• Ejection fraction < 50% assessed by MUGA or ECHO scan within 14 days of Day 1

• Known confirmed diagnosis of HIV infection or active viral hepatitis

• Received any investigational agent within 30 days prior to Day 1

• Any surgical procedure, excluding central venous catheter placement, bone marrow biopsy or other minor procedures (eg skin biopsy) within 14 days of Day 1

• Unwilling or unable to comply with the protocol

• Known malignant disease of the central nervous system

• Any pulmonary infiltrate including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved

• Patients with prior midostaurin (PKC412) treatment are excluded

• Patients receiving any other investigational agents or have received other investigational agents within 30 days of enrollment

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine