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

NCT01130662 | Completed Phase 1 DMC

• 2 other identifiers: 12010CPCK412AUS06T
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia; AML; Relapsed AML; Refractory AML

Outcome Measures

Primary Outcomes (1)

• To determine a tolerated dose of the combination of decitabine and midostaurin as induction and consolidation in patients ≥ 60 years with newly diagnosed AML not eligible for standard induction or adult patients with relapsed/refractory disease.

  3 months per patient

Secondary Outcomes (1)

• Explore potential association between clinical response and FLT-3 status in patients treated in each cohort; assess toxicity of combination in each dosing cohort

  3 months per patient

Study Arms (1)

Decitabine Midostaurin combination

EXPERIMENTAL

Drug: combination therapy using decitabine and midostaurin

Interventions

combination therapy using decitabine and midostaurin DRUG

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.

Also known as: Dacogen, PKC412

Decitabine Midostaurin combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kansas: lead
• Novartis: collaborator

Study Sites (1)

University of Kansas Medical Center, Westwood Campus

Kansas City, Kansas, 66205, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

midostaurin; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Casey Williams, PharmD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2010
• First Posted: May 26, 2010
• Study Start: March 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: March 26, 2013

Record last verified: 2013-03

Locations

US (1)