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

This is an interventional treatment trial for Acute Myeloid Leukemia With Gene Mutations Read More

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