An Open-label Phase II Study of Lorvotuzumab Mertansine

Inclusion Criteria: 1. 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). 2. Any level of CD56 expression will be considered sufficient for enrollment on this study. 3. Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed. 4. Age \>/=18 years 5. Eastern Cooperative Oncology Group (ECOG) Performance Status \</= 2 6. Adequate organ function: total bilirubin \</= 2 times upper limit of normal (x ULN) (\</=3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \</= 2.5 x ULN (\</= 5.0 x ULN if considered to be due to leukemic involvement); serum creatinine \</= 2 x ULN, amylase and lipase \</=2 x ULN . 7. In the absence of rapidly progressing disease and after discussion with the Principal Investigator (PI), the interval from prior treatment to time of IMGN901 administration will be at least 2 weeks or at least 5 half-lives for cytotoxic/noncytotoxic agents. The half-life be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document. 8. continuation from criteria #7: For prior monoclonal antibody therapy the interval from prior monoclonal antibody treatment to time of IMGN901 administration will be at least 2 weeks. The use of chemotherapeutic or anti-leukemic agents other than hydroxyurea (as defined in the protocol) is not permitted during the study with the exception of intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the PI. Hydroxyurea is allowed prior to the initiation of IMGN901 and during the first 3 cycles, either prior to or concomitantly with IMGN901 administration initially to control Leukocytosis. 9. Women of childbearing potential must practice contraception. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study. 10. Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment 11. Patients must provide written informed consent. 12. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to screening). 13. continued from criteria #12: For female patients on the study, the vasectomized male partner should be the sole partner for that patient Combination of any of the two following (a+b or a+c or b+c) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository In case of use of oral contraception, women should have been stable on the same pill before taking study treatment. Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction 14. continued from criteria #13 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. Exclusion Criteria: 1. Patients with known allergy or hypersensitivity to IMGN901. 2. Patients who have previously been treated with IMGN901. 3. Patients with symptomatic central nervous system (CNS) leukemia or patients with poorly controlled central nervous system leukemia. 4. Peripheral neuropathy \>grade 2. 5. Active or clinically symptomatic chronic pancreatitis or disease affecting pancreas. 6. Neurologic disease including multiple sclerosis, Eaton-Lambert syndrome, demyelination. 7. 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. 8. Patients with known Human Immunodeficiency Virus seropositivity will be excluded. 9. 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. 10. 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. 11. Patients with any concurrent severe and/or uncontrolled medical condition or active uncontrolled systemic infection as determined by the investigator. 12. Patients who have had any major surgical procedure within 14 days of Day 1. 13. Patients unwilling or unable to comply with the protocol.