Phase 1 Study of SL-401 in Combination with Azacitidine and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia (AML) and in Treatment-Naive Subjects with AML Not Eligible for Standard Induction and in Subjects with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or SL-401 in Combination with Azacitidine in Subjects with High-Risk Myelodysplastic Syndrome (MDS)

Protocol # :
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Blastic Plasmacytoid Dendritic Cell Neoplasm
Disease Sites
Other Hematopoietic
Myeloid and Monocytic Leukemia
Principal Investigator
Lane, Andrew

Trial Description

This research study is studying a drug as a possible treatment for diagnosis of AML, BPDCN
and high-risk MDS.

The interventions involved in this study are:

- SL-401

- Azacitidine

- Venetoclax

Eligibility Requirements

Inclusion Criteria:

Histologically confirmed diagnosis of acute myeloid leukemia (AML) [Cohort B] or
myelodysplastic syndrome (MDS) [Cohort A] or BPDCN [Cohort C] per 2016 WHO criteria

CD123 / IL3RA expression on the subject's AML or MDS blasts or BPDCN cells 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) [Cohort B]


Age >= 18 years with treatment-naïve AML who decline intensive induction chemotherapy or
who are unfit due to co-morbidity or other factors (see APPENDIX A for unfitness
definitions) (hydroxyurea is not considered a prior treatment regimen) [Cohort B]


Age >= 18 years with MDS and > 10% myeloblasts in the bone marrow [Cohort A]


Age >= 18 years with relapsed or refractory BPDCN (hydroxyurea is not considered a prior
treatment regimen) [Cohort C]

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

[Cohorts B and C] WBC < 20,000 / uL on day of first therapy, cytoreduction may be achieved
using hydroxyurea

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 protocol treatment.

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 protocol treatment.

Exclusion Criteria:

Prior treatment with venetoclax [Cohorts B or C], unless it was last taken >2 months before
protocol therapy

Diagnosis of acute promyelocytic leukemia

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

Hematopoietic stem cell transplantation (HSCT) within 60 days of screening or active graft

Active CNS involvement by AML or BPDCN. Screening lumbar puncture (LP) required for
patients with BPDCN. If history of treated CNS involvement, must have had two consecutive
negative LPs since last CNS involvement, which may include the screening LP

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, azacitidine, and venetoclax
(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,
azacitidine, and venetoclax.

Patients with uncontrolled infection shall not be enrolled until infection is treated and
brought under control. Patients with active infection are permitted to enroll provided that
the infection is controlled

[Cohorts B and C] Patients with gastrointestinal (GI) tract disease causing the inability
to take oral medication, malabsorption syndrome, a requirement for intravenous (IV)
alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI
disease (e.g., Crohn's disease, ulcerative colitis)

[Cohorts B and C] Patients on strong CYP3A inducers within 7 days of first dose of study