Tagraxofusp in Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm or Acute Myeloid Leukemia

Inclusion Criteria

• The patient has a diagnosis of AML (Protocol Stages 1 and 2) or BPDCN (Protocol Stages 1-4) according to WHO classification (AML; excluding acute promyelocytic leukemia [APL, FAB M3]) or confirmed by hematopathology (BPDCN) (Facchetti et al. 2008).
• The patient must meet one of the following (a) or (b) or (c):
• Has evidence of persistent or recurrent AML (Protocol Stages 1 and 2) in the peripheral blood and/or bone marrow that is refractory to, or has relapsed from, their most recent prior line of treatment.
• A prior line of treatment is considered an induction regimen if it involves an approved or investigational cytotoxic chemotherapy agent, biological agent, and/or hypomethylating agent administered alone or in a combination regimen, with the intent to induce robust cytoreduction (i.e., CR).
• The previous induction regimen may have been a SCT with intent to induce a CR.
• Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but are not counted as a line of treatment.
• Hydroxyurea will not be considered a prior line of treatment.
• Has previously untreated AML (Protocol Stages 1 and 2) and is considered to be at high risk for disease progression and/or is unlikely to derive more than transient benefit from standard therapy by having at least one of the following:
• Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., inversion 16, t[16;16], t[8;21], t[15;17]), and not a candidate for SCT in their current disease state.
• AML with antecedent hematological disease (e.g., MDS, myelofibrosis, polycythemia vera) and not a candidate for SCT.
• Has histological and/or cytological evidence of BPDCN by pathologic assessment at the investigative site according to WHO classification (Facchetti et al. 2008) by a pathologist with expertise in hematologic malignancies, that can be measured for treatment response and is either:
• Previously untreated (i.e., first-line) (Protocol Stages 2-4).
• Persistent or recurrent in the peripheral blood, bone marrow, spleen, lymph nodes, skin, or other sites after previous treatment with at least 1 line of systemic therapy for BPDCN, e.g., stem cell transplant or chemotherapy (Protocol Stages 1, 2, and 4). A pathology specimen must be available for central pathology review for all BPDCN patients enrolled in Protocol Stages 2-4.
• The patient is ≥ 18 years old.
• The patient has an ECOG performance score (PS) of 0-2.
• The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:
• Left ventricular ejection fraction (LVEF) ≥ institutional lower limit of normal as measured by MUGA scan or 2-D ECHO within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead ECG
• Serum creatinine ≤ 1.5 mg/dl
• Serum albumin ≥ 3.2 g/dl
• Bilirubin ≤ 1.5 mg/dl
• AST and ALT ≤ 2.5 times the upper limit of normal (ULN)
• If the patient is a woman of child bearing potential (WOCBP), she has had a negative serum or urine pregnancy test within 1 week prior to treatment.
• The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.
• The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
• The patient (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study, and continue to use acceptable contraceptive methods for 2 months after the last infusion of Tagraxofusp.

Exclusion Criteria

• The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB M3).
• The patient has persistent clinically significant toxicities Grade ≥ 2 from previous chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests (as mandated in the inclusion criteria)).
• The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study e