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

PRIMARY OBJECTIVES:

I. To determine the efficacy and safety of maintenance midostaurin (a fms related tyrosine
kinase 3 [FLT3] inhibitor) for elderly patients with FLT3-internal tandem duplication
(ITD)/tyrosine kinase domain (TKD) mutated acute myeloid leukemia (AML) who were previously
enrolled on study HEMAML0022/CPKC412AUS27T and have then undergone allogeneic transplant.

SECONDARY OBJECTIVES:

I. To determine whether maintenance midostaurin after allogeneic transplant decreases the
relapse rate in patients with FLT3-ITD/TKD mutated AML.

OUTLINE:

Beginning 30 days post-hematopoietic cell transplantation (HCT), patients receive midostaurin
orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12
courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 1
year.

Inclusion Criteria:

- Elderly patients with FLT3-mutated AML who were previously enrolled on the
CPKC412AUS27T study are eligible for enrollment

- Prior enrollment in 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) and alanine aminotransferase (ALT) =< 2.5 times upper
limit of normal (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 two-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, either

- 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 III-IV

- 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 III or IV

- 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)

- Nursing (lactating) women

- Women of child-bearing potential, including pregnant