An Open-label Phase II Study of Lorvotuzumab Mertansine

Inclusion Criteria

• Patients with CD56 expressing hematological malignancy, as follows: Cohort 1: CD56 expressing hematological malignancies including but not limited to AML, high-risk myelodysplastic syndrome (MDS), natural-killer leukemia, acute lymphoblastic leukemia, accelerated and blast-phase chronic myelocytic leukemia (CML) who have failed prior therapy or for which no standard therapy exists.Cohort 2: Patients with MF (either primary MF, post-polycythemia MF, or post-essential thrombocythemia MF) and CD56 expression who have been on ruxolitinib or JAK-inhibitor therapy for at least 12 weeks and deemed refractory or sub-optimal responders in the opinion of the treating physician.Cohort 3: Patients with pathological diagnosis of BPDCN with CD56 expression (frontline and relapsed/refractory).
• Any level of CD56 expression will be considered sufficient for enrollment on this study.
• Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed.
• Age >/=18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status grade 2.
• Active or clinically symptomatic chronic pancreatitis or disease affecting pancreas.
• Neurologic disease including multiple sclerosis, Eaton-Lambert syndrome, demyelination.
• Significant cardiac disease including myocardial infarction or unstable angina within 6 months, uncontrolled hypertension despite medical therapy (defined as blood pressure >160/110 in spite of adequate medical therapy), active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, stroke within preceding 6 months.
• Patients with known Human Immunodeficiency Virus seropositivity will be excluded.
• Known to be positive for hepatitis B by surface antigen expression. Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months). Known to be active CMV infection or herpes zoster infection.
• Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive B-human chorionic gonadotropin (HCG) laboratory test.
• Patients with any concurrent severe and/or uncontrolled medical condition or active uncontrolled systemic infection as determined by the investigator.
• Patients who have had any major surgical procedure within 14 days of Day 1.
• Patients unwilling or unable to comply with the protocol.