Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.

2. Age >/=18 years at the time of signing the informed consent form.

3. Diagnosis of AML [other than acute promyelocytic leukemia (APL)] with
refractory/relapsed disease; patients with relapsed/refractory high-risk
[(intermediate-2 or higher by International Prognostic Scoring System (IPSS) and/or
>/= 10% blasts)]. MDS will also be eligible. (Treatment approach for
relapsed/refractory AML is very similar to that of high risk MDS).

4. All non-hematological toxicity of previous cancer therapy should have resolved to grade1 (except alopecia or other toxicities not involving major organs).

5. Eastern Cooperative Oncology Group (ECOG) performance status of
6. Laboratory test results within these ranges: Serum creatinine estimated glomerular filtration rate or creatinine clearance >/= 20 ml/min; Total
bilirubin aminotransferase (ALT)
7. Women of childbearing potential must be practicing a highly effective method of birth
control consistent with local regulations regarding the use of birth control methods
for subjects participating in clinical studies: eg, established use of oral, injected
or implanted hormonal methods of contraception; placement of an intrauterine device or
intrauterine system; barrier methods: condom with spermicidal
foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps)
with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the
vasectomized partner should be the sole partner for that subject); true abstinence
(when this is in line with the preferred and usual lifestyle of the subject) during
and after the study (3 months after the last dose of daratumumab for women).

8. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
must also not donate sperm during the study and for 3 months after receiving the last
dose of study drug.

9. AML relapse > 6 months since autologous or allogeneic stem cell transplantation,
provided there is no active graft-versus-host disease (GVHD) > grade 1; no treatment
with high dose steroids for GVHD (up to 20 mg Prednisolone or equivalent); no
treatment with immunosuppressive drugs with the exception of low dose cyclosporine and
tacrolimus (blood levels of 0.5-0.6 µg/mL).

Exclusion Criteria:

1. Pregnant or breast feeding females.

2. Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (exception
hydroxyurea). Use of hydroxyurea to control proliferative disease will be allowed
prior to starting therapy on study and for 7 days during cycle 1-3 (Maximum daily dose
of 7gm).

3. Subject has received daratumumab or other anti-CD38 therapies previously.

4. Subject has received a cumulative dose of corticosteroids more than the equivalent of
>/= 140 mg of prednisone within the 2 week period before Cycle 1, Day 1.

5. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced
Expiratory Volume in 1 second (FEV1) <50% of predicted normal. NOTE: FEV1 testing is
required for patients suspected of having COPD and subjects must be excluded if FEV1
<50% of predicted normal.

6. Subject has a history of another malignancy within 5 years before Cycle 1, Day 1
(exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ
of the cervix, or malignancy that in the opinion of the investigator, with concurrence
with the IND office and supporter's medical monitor, is considered cured with minimal
risk of recurrence).

7. Subject is known to be seropositive for human immunodeficiency virus (HIV) or
hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or
antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc,
respectively]) or hepatitis C (anti-HCV antibody positive or HCV-RNA quantitation
positive).

8. Subject has clinically significant cardiac disease, including: myocardial infarction
within 1 year before Cycle 1, Day 1, or unstable or uncontrolled disease/condition
related to or affecting cardiac function (eg, unstable angina, congestive heart
failure, New York Heart Association Class III-IV); cardiac arrhythmia (CTCAE Version
4.03 Grade 2 or higher) or clinically significant ECG abnormalities; screening 12-lead
ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470
msec.

9. Subject has known severe allergies, hypersensitivity, or intolerance to monoclonal
antibodies or human proteins, or their excipients (refer to the latest version of the
Investigator Brochure), or known sensitivity to mammalian-derived products.

10. Subject has any concurrent medical condition or disease (eg, active systemic
infection, laboratory abnormalities) that is likely to interfere with study procedures
or results, or that in the opinion of the investigator would constitute a hazard for
participating in this study.

11. Exclude patients with known Kell antibodies.