What's the purpose of this trial?
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:
This trial is currently open and accepting patients.
What will happen during the trial?
You may be able to join this trial if you:
The following criteria is a partial list of reasons why patients may be
eligible to participate in this clinical trial. Further evaluation with a medical professional is
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.
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 versus-host-disease
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 treatment.
Additional Trial Information
Enrollment: 72 patients (estimated)
Trial Sponsor: Dana-Farber Cancer Institute
Trial Collaborator: Stemline Therapeutics, Inc.
SparkCures Identifier: 1536