Selinexor (KPT-330) in Older Patients With Relapsed AML

This is a randomized, multicenter, open-label phase 2 study of the SINE compound, selinexor
given orally versus restricted investigator choice (i.e., one of three potential salvage
therapies).

Patients who have never been transplant eligible, are currently deemed unfit for intensive
chemotherapy, ≥ 60 years old, who have AML (except Acute Promyelocytic Leukemia: APL, AML M3)
after one prior treatment of either hypomethylating agent or a regimen including Ara-C, and
are meeting the inclusion and exclusion criteria will be randomized to receive either oral
selinexor or physician's choice (one of three potential treatments: best supportive care
(BSC) alone, or BSC + hypomethylating agent, or BSC + low dose Ara-C until disease
progression, death or intolerance has occurred.

Inclusion Criteria:

- Age ≥ 60 years with relapsed or refractory AML of any type except for acute
promyelocytic leukemia (APL; AML M3), after at least 1 prior AML therapy , who have
never undergone, and who are not currently eligible for, stem cell transplantation,
and are currently deemed unfit for intensive chemotherapy.

- ECOG ≤ 2.

- Must have available archival or recently acquired bone marrow biopsy/aspiration or
tumor tissue for central review to be eligible.

- Relapsed or refractory AML, defined as either: recurrence of disease after a complete
remission (CR), or failure to achieve CR with initial therapy.

- Must have received at least 1 prior line of AML therapy given at standard doses and
must have progressed after their most recent therapy. Prior therapy must have
included: a hypomethylating agent with at least 2 cycles.

- At least 2 weeks must have elapsed since the last anti-leukemia treatment (with the
exception of hydroxyurea) before first dose in this study.

Exclusion Criteria:

- Treatment with any investigational agent within 3 weeks prior to first dose in this
study.

- Presence of central nervous system (CNS) leukemia.

- In blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic
syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML
therapy.

- 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.

- Concurrent active malignancy under treatment.

- 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 HIV infection.

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

- Patients whose AML is classified as favorable according to the European LeukemiaNet
(ELN) disease risk assessment.