Status:
TERMINATED
Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Lead Sponsor:
David Iberri
Conditions:
Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults
AML (Adult) With 11q23 (MLL) Abnormalities
Eligibility:
All Genders
60+ years
Phase:
PHASE2
Brief Summary
This phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (AML) in older patients.
Detailed Description
Treatment with decitabine, a cytidine analog, then midostaurin, a multi-target protein kinase inhibitor (PKI), may stop the growth of cancer cells by blocking some of the enzymes needed for cell growt...
Eligibility Criteria
Inclusion
- Newly-diagnosed acute myeloid leukemia (AML) per the World Health Organization \[WHO\] 2008 classification \[except t (15; 17)\], including:
- De novo AML
- Secondary AML
- Secondary AML arising from previously-diagnosed myelodysplastic syndromes (MDS) treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) (ie, decitabine or azacitidine)
- FLT3-ITD mutation confirmed in bone marrow aspirate
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Serum bilirubin ≤ 2.5 ULN
- Serum creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 50 mL/min
- Ejection fraction ≥ 50% by echocardiogram
- Unwillingness or inability to receive conventional chemotherapy
- Ability to understand and the willingness to sign a written informed consent document
- Ability to adhere to the study visit schedule and other protocol requirements
- Life expectancy \> 2 months
Exclusion
- Receiving concomitant treatment with other anti-neoplastic agents (EXCEPTION: hydroxyurea). Prior treatment with DNMTi therapy (ie, decitabine or azacitidine) for MDS is allowed
- Received anti-neoplastic treatment within 4 weeks prior to enrollment (EXCEPTION: hydroxyurea)
- Received any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of study day 1
- Received any investigational agent within 4 weeks prior to enrollment
- Previous or current history of a myeloproliferative disease
- Known active central nervous system (CNS) malignancy
- Any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition which could compromise participation in the study (eg, uncontrolled diabetes; cardiovascular disease including congestive heart failure; myocardial infarction within 6 months with poorly controlled hypertension; chronic renal disease; active uncontrolled infection)
- Active opportunistic infection or treatment for opportunistic infection within 4 weeks of first day of study drug dosing
- Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine
- Impaired cardiac function including any of the following:
- Screening electrocardiogram (ECG) with a corrected QT interval (QTc) \> 450 msec
- Bradycardia defined as heart rate (HR) \< 50 beats per minute (bpm)
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Patients with myocardial infarction or unstable angina \< 3 months prior to starting study drug
- Congestive heart failure (CHF) New York (NY) Heart Association class 3 or 4
- Inability to swallow or absorb drug
- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation
- Unwillingness or inability to comply with the protocol
- Pregnant
- nursing (lactating)
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using highly effective methods of contraception during dosing and for 3 months after midostaurin medication; highly effective contraception methods as follows:
- Total abstinence, when this is in line with the preferred and usual lifestyle of the subject \[periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\]
- Female sterilization (surgical bilateral oophorectomy with or without hysterectomy; or tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, reproductive status must be confirmed by follow-up hormone level assessment
- Male sterilization, at least 6 months prior to screening (for female subjects on the study, the vasectomized male partner should be the sole partner for that subject)
- Combination of any two of the following (a+b or a+c, or b+c):
- Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), eg, hormone vaginal ring or transdermal hormone contraception. For oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Key Trial Info
Start Date :
June 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 31 2016
Estimated Enrollment :
13 Patients enrolled
Trial Details
Trial ID
NCT01846624
Start Date
June 1 2013
End Date
August 31 2016
Last Update
September 27 2018
Active Locations (1)
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1
Stanford University School of Medicine
Stanford, California, United States, 94305