Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Not Recruiting

Trial ID: NCT01846624


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.

Official Title

A Phase 2 Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia

Stanford Investigator(s)

David Iberri
David Iberri

Clinical Assistant Professor, Medicine - Hematology


Inclusion Criteria:

   - 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 Criteria:

   - 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:

   - 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

      - 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

      - 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


drug: decitabine

drug: midostaurin

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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