This trial is active, not recruiting.

Conditions acute myeloid leukemia (aml) with multilineage dysplasia following myelodysplastic syndrome, in adults, aml (adult) with 11q23 (mll) abnormalities, aml (adult) with del(5q), aml (adult) with inv(16)(p13;q22), aml (adult) with t(16;16)(p13;q22), aml (adult) with t(8;21)(q22;q22), secondary aml (adult), untreated aml (adult)
Treatments decitabine, midostaurin
Phase phase 2
Sponsor Bruno C. Medeiros
Collaborator National Cancer Institute (NCI)
Start date June 2013
End date December 2020
Trial size 36 participants
Trial identifier NCT01846624, HEMAML0022, NCI-2013-00868


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year.
decitabine 5-aza-dCyd
Given IV
midostaurin N-benzoyl-staurosporine
Given PO

Primary Outcomes

Complete remission (CR) rate
time frame: Up to 1 year

Secondary Outcomes

Median overall survival (OS)
time frame: Up to 2 years
Median duration of response
time frame: Up to 2 years

Eligibility Criteria

Male or female participants at least 60 years old.

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: 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 III or IV - 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

Additional Information

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
Principal investigator Bruno C. Medeiros
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 growth.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Stanford University.
Location data was received from the National Cancer Institute and was last updated in June 2016.