Midostaurin in Treating Older Patients With Mutated Acute Myeloid Leukemia Post-Transplant

INCLUSION CRITERIA

* Elderly patients with FLT3-mutated acute myeloid leukemia (AML)
* Prior enrollment in Stanford study IRB-25737
* In continued complete remission
* ≥ 30 days but ≤ 90 days post allogeneic hematopoietic cell transplant (HCT); treatment on this study protocol must begin before day 90 post-HCT
* Absolute neutrophil count (ANC) ≥ 1000 cells/uL
* Hemoglobin ≥ 8.0 g/dL and not requiring regular transfusions
* Platelets ≥ 50,000 cells/uL and not requiring regular transfusions
* Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
* Alanine aminotransferase (ALT) ≤ 2.5 X ULN
* Serum bilirubin ≤ 2.5 times ULN
* Ability to give written informed consent, including via legally authorized representative
* Corrected QT (QTc) ≤ 450 msec
* Ejection fraction (EF) ≥ 45% by 2-dimensional transthoracic echocardiography (TTE) or multiple-gated acquisition (MUGA)
* Sexually active males, including vasectomized males, must agree via informed consent to use a condom during vaginal, anal, or oral intercourse, while taking midostaurin and for 5 months after stopping midostaurin
* Females must have or be:

  * Negative pregnancy test, within 21 days of the first dose of midostaurin OR
  * Not of childbearing potential as follows:

    * Has undergone a hysterectomy or bilateral oophorectomy;
    * Has not had menses at any time in the preceding 24 consecutive months

EXCLUSION CRITERIA

* Uncontrolled acute graft-vs-host disease (GVHD) grade 3 to 4
* Uncontrolled active infection
* Evidence of active AML (eg, circulating peripheral blasts on complete blood count)
* Known confirmed diagnosis of human immunodeficiency virus (HIV) infection
* Known confirmed diagnosis of active viral hepatitis
* QTc \> 450 msec
* Congenital long QT syndrome
* History of presence of sustained ventricular tachycardia, history of ventricular fibrillation or torsades de pointes
* Bradycardia defined as heart rate (HR) \< 50 beats per minute (bpm)
* Bifascicular block (right bundle branch block plus left anterior hemiblock)
* Congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4
* Cardiac ejection fraction (EF) \< 45% within 28 days prior to starting cycle 1
* Other known malignancy (except carcinoma in situ)
* Other concurrent severe and/or uncontrolled medical condition which could compromise participation in the study, eg:

  * Uncontrolled diabetes
  * Chronic active pancreatitis
  * Myocardial infarction within 6 months
  * Poorly-controlled hypertension
  * Chronic kidney disease
* Received any investigational agent within 30 days prior to day 1
* Antineoplastic chemotherapy or radiotherapy within 28 days prior to cycle 1
* No plans for concurrent chemotherapy while on study (exception: antineoplastic drugs used as part of GVHD prophylaxis or treatment)
* Any surgical procedure, excluding central venous catheter placement, bone marrow biopsy or other minor procedures (eg, skin biopsy) within 14 days of day 1
* Unwillingness or inability to comply with the protocol
* Known malignant disease of the central nervous system
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin
* Concomitant use of strong inhibitors of cytochrome P450 family 3 subfamily A member 4 (CYP3A4)
* Pregnant or lactating
* Women of child-bearing potential