Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of selinexor in patients with hematologic
malignancies, especially acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), after
allogeneic (allo)-stem cell transplant (SCT).

SECONDARY OBJECTIVES:

I. To evaluate the toxicities of selinexor as maintenance treatment after allo-SCT.

II. To determine the incidence of non-relapse mortality. III. To determine 2 years post SCT
progression-free survival (PFS) and overall survival rates.

IV. To determine the incidence of acute and chronic graft-versus-host disease (GVHD).

V. To assess lymphoid and myeloid chimerism post transplantation.

TERTIARY OBJECTIVES:

I. To analyze donor immune re-constitution after allo-SCT with selinexor maintenance.

II. To monitor minimal residual disease (MRD) by Wilms tumor 1 (WT1) polymerase chain
reaction (PCR) during selinexor treatment in AML/MDS patients.

III. To characterize the physiopathology of the leukemia initiating cells (LIC) at the time
of disease relapse on selinexor maintenance and compare that at initial diagnosis of the
disease.

OUTLINE: This is a dose-escalation study.

Beginning on day 60-100 after allo-SCT without evidence of GVHD above grade 1 and disease
relapse with stable hematopoietic recovery, patients receive selinexor orally (PO) on day 1
of each week or on days 1 and 3 of weeks 1-3. 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 for 1 year.

Inclusion Criteria:

- Signed, written informed consent in accordance with federal, local, and institutional
guidelines

- Patients underwent allo-SCT with intermediate risk and high risk AML and high risk MDS
(defined by American Society for Blood and Marrow Transplantation [ASBMT] criteria),
who are within 60 to 100 days after allo-SCT

- There is no evidence of disease relapse at the time of screening, and minimal residual
disease (MRD) is acceptable

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Absolute neutrophil count (ANC) > 1000 uL

- Platelets >= 20,000 without platelet transfusion

- Creatinine clearance > 30 cc/min calculated using the Cockcroft and Gault (1976)
formula or measured

- Total bilirubin =< 2 mg/dl unless high indirect bilirubin is due to a congenital
disorder

- Transaminases (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) =<
2.0 x upper limit of normal (ULN)

- Prothrombin time (PT) and partial thromboplastin time (PTT) =< 2 x ULN

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures

- It is important patients understand the need to use birth control while on this study;
female patients of child-bearing potential must agree to use dual methods of
contraception and have a negative serum pregnancy test at screening (< 3 days prior to
first dose), male patients with partners of childbearing potential must agree to use
effective contraception during the study period and a period of 3 months after the
last dose of study drug; for both male and female patients, effective methods of
contraception must be used throughout the study and for three months following the
last dose

Exclusion Criteria:

- Patients with acute GVHD grade II-IV

- Treatment with any investigational agent within three weeks prior to first dose in
this study

- Major surgery within 2 weeks of first dose of study drug; patients must have recovered
from the effects of any surgery performed greater than 2 weeks previously

- Patient has a concurrent active malignancy under treatment

- Unstable cardiovascular function:

- Symptomatic ischemia, or

- Uncontrolled clinically significant conduction abnormalities (i.e., ventricular
tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular
(AV) block or asymptomatic left anterior fascicular block/right bundle branch
block (LAFB/RBBB) will not be excluded), or

- Congestive heart failure (CHF) NYHA class >= 3, or

- Myocardial infarction (MI) within 3 months

- Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals
within one week prior to first dose; infections controlled on concurrent
anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional
guidelines are acceptable

- Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be
positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen)

- Known human immunodeficiency virus (HIV) infection

- Any medical condition which, in the investigator's opinion, could compromise the
patient's safety

- Patients unable to swallow tablets or patients with malabsorption syndrome, or any
other disease significantly affecting gastrointestinal function