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)
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
• 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) \[Cohort B\]
• OR
• 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) \[Cohort B\]
• OR
• Age \>= 18 years with MDS and \> 10% myeloblasts in the bone marrow \[Cohort A\]
• OR
• 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.