Selinexor With Induction, Consolidation, and Maintenance Therapy in Treating Older Patients With Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. Assess the feasibility of adding selinexor to induction, consolidation and maintenance
therapy of elderly acute myeloid leukemia (AML) patients.

SECONDARY OBJECTIVES:

I. To assess the safety of administering selinexor under the proposed study regimen.

II. To assess response and survival endpoints of patients receiving the proposed study
regimen.

III. To assess the rate of allogeneic stem cell transplantation.

OUTLINE:

INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7, daunorubicin
hydrochloride IV on days 1-3, and selinexor orally (PO) twice weekly from day 1. Treatment
continues for 14 days in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION THERAPY: Patients whose disease has not responded receive cytarabine IV on days
1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment
continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Patients in remission receive cytarabine IV every 12 hours on days 1,
3 and 6, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to
3 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients who have had a response and have not gone on to transplant
receive selinexor PO twice weekly. Treatment continues for 4 weeks in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 14 days and then every 3
months for up to 1 year.

Inclusion Criteria:

- Patients must have histologically or cytologically documented newly diagnosed acute
myeloid leukemia (non-acute promyelocytic leukemia [APL]) that has not yet been
treated; hydrea and all-trans retinoic acid (ATRA) previous treatments are acceptable

- Hydroxyurea may be used to control leukocytosis and can be taken until start of
therapy

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 and fit for
induction therapy in the opinion of the treating physician

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X institutional upper limit of normal

- Bilirubin =< 2 X ULN (3 X if known history of Gilbert's syndrome)

- Creatinine =< 2 mg/dL

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Ability to understand and the willingness to sign an Institutional Review Board
(IRB)-approved informed consent document

Exclusion Criteria:

- Patients who have received any therapy other than hydroxyurea or ATRA with the purpose
of treating their AML or patients with acute promyelocytic leukemia are not eligible

- Patients having received prior radiotherapy, treatment with cytotoxic agents,
treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy
within the 4 weeks prior to treatment with selinexor, or those who have not fully
recovered from the acute, non-hematological, non-infectious toxicities of any prior
treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned
to baseline status as noted before most recent treatment)

- Patients with another active malignancy that requires treatment excluding non-melanoma
skin cancers

- Patients that have received a chemotherapy regimen with stem cell support in the
previous 6 months

- Patients with known central nervous system involvement should be excluded from this
clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to selinexor

- Uncontrolled concurrent illness including, but not limited to symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements

- Patients with known human immunodeficiency virus (HIV) infection

- Pregnant women are excluded from this study; breastfeeding should be discontinued