SL-401 in Combination With Azacitidine in Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

This research study is a Phase I clinical trial, which tests the safety of an investigational
intervention and also tries to define the appropriate dose of the investigational
intervention to use for further studies. "Investigational" means that the intervention is
being studied.

The FDA (the U.S. Food and Drug Administration) has approved Azacitidine as a treatment
option for this disease. SL-401 is an investigational drug, which means it is not approved by
the FDA as a treatment for any disease.

In this research study, the study drug SL-401 will be combined with the standard dose of
azacitidine. The goal of this research study is to try and determine the safest, highest dose
of study drug, SL-401, in combination with azacitidine that can be given to patients with AML
or high-risk MDS. SL-401 works by stopping or slowing the growth of cancer stem cells, which
are the undeveloped cells which can develop into cancer cells. The goals of this research
study are to look at if this combination works to help treat cancer and if there is any
lasting effect of this combination . This study will also look at how the SL-401, in
combination with azacitidine, affects certain proteins in the blood and bone marrow. SL-401
has been given to patients with AML and MDS in the past, but this is the first time it will
be given in combination with another drug.

Inclusion Criteria:

- Histologically confirmed diagnosis of acute myeloid leukemia (AML) or myelodysplastic
syndrome (MDS) per 2016 WHO criteria

- CD123 / IL3RA expression on the subject's AML, determined locally within 3 months of
first protocol treatment

- Age >= 18 years with relapsed or refractory AML (hydroxyurea is not considered a prior
treatment regimen) OR Age >= 18 years with treatment-naïve AML who decline intensive
induction chemotherapy or who are unfit due to co-morbidity or other factor
(hydroxyurea is not considered a prior treatment regimen) OR Age > 18 years with MDS
and >= 10% myeloblasts in the bone marrow

- ECOG performance status 0, 1, or 2

- Adequate organ function as defined by:

- Albumin > 3.2 g/dL (in the absence of receipt of intravenous albumin in the
previous 72 hours)

- Serum creatinine < 1.5x ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN

- Total bilirubin < 1.5x ULN (if thought to be > 1.5x ULN due to Gilbert's disease
or the patient's AML, must discuss with the PI)

- Creatine phosphokinase (CPK) < 2.5x ULN

- Left ventricular ejection fraction > institutional lower limit of normal by MUGA
scan or echocardiogram within 30 days of first protocol treatment

- Ability to understand and the willingness to sign a written informed consent document.

- Able to adhere to study visit schedule and other protocol requirements including
follow-up for survival assessment

- Women of child-bearing potential must agree to use adequate contraception for the
duration of study participation and for 2 months after completion of SL-401 and
azacitidine administration. Men treated or enrolled on this protocol must also agree
to use adequate contraception for the duration of study participation and 2 months
after completion of SL-401 and azacitidine administration.

Exclusion Criteria:

- Prior treatment with a hypomethylating agent (including but not limited to azacitidine
or decitabine) unless last treatment with hypomethylating agent was >3 months prior to
start of protocol treatment OR has received <2 cycles of hypomethylating agent without
disease progression during those <2 cycles and last dose was not within 14 days of
first protocol treatment

- Prior treatment with SL-401

- Diagnosis of acute promyelocytic leukemia

- Received treatment with chemotherapy, radiation, or biologic cancer therapy within 14
days of first protocol treatment. Prior and concurrent hydroxyurea is permitted.

- Hematopoietic stem cell transplantation (HSCT) within 60 days of screening, or receipt
of immunosuppressive therapy for graft-versus-host disease treatment or prophylaxis
within 30 days of screening, or active graft-versus-host-disease

- Known CNS involvement by AML

- Known positive status for HIV infection; known active hepatitis B or hepatitis C
infection

- Clinically significant cardiopulmonary disease including uncontrolled or NYHA class 3
or 4 congestive heart failure, uncontrolled angina, uncontrolled hypertension,
uncontrolled arrhythmia, myocardial infarction or stroke within 6 months of first
protocol treatment, or QTc > 480 ms

- Patients with known active advanced malignant solid tumors are excluded (except for
basal or squamous skin cancers, or carcinomas in situ). Patients with additional
hematologic malignancies that require treatment are excluded.

- Pregnant women are excluded from this study because there is an unknown but potential
risk for adverse events in the developing fetus with SL-401 and azacitidine (negative
urine or serum pregnancy test required within 14 days of Cycle 1, Day 1). Because
nursing infants have unknown potential for adverse events secondary to treatment of
the mother, breastfeeding should be discontinued if the mother is treated with SL-401
and azacitidine.

- Infection is a common feature of AML. Patients with active infection are permitted to
enroll provided that the infection is controlled. Patients with uncontrolled infection
shall not be enrolled until infection is treated and brought under control