Daratumumab and Donor Lymphocyte Infusion in Treating Participants With Relapsed Acute Myeloid Leukemia After Stem Cell Transplant

Inclusion Criteria:

* AML relapse following Allo-HSCT (Morphological relapse, or MRD positive verified by flow cytometry, cytogenetics, and molecular mutations)
* Relapsed/Refractory AML must not be candidates for available therapies known to be effective for treatment of their AML.
* MDS transformed to AML following Allo-HCT
* Patients who received a 10/10 HLA-matched allogeneic HCT either from sibling donors or unrelated donors or atleast a 5/10 haploidentical transplant.
* Engraftment must have occurred as defined by platelet (PLT) count \> 20,000/µL and ANC

  * 0.5
* Eastern Cooperative Oncology Group (ECOG) performance status \< 3
* Creatinine clearance \> 40 ml/min (calculated or measured)
* Aspartate aminotransferase (AST) \< 3 x upper limit of normal (ULN), alanine aminotransferase (ALT) \< 3 x ULN
* Total bilirubin \< 1.5 x ULN
* Off calcineurin inhibitors for at least 2 weeks
* Prednisone dose ≤ 20 mg/day
* Patients with proliferative disease can be cytoreduced with cytotoxic chemotherapy at Investigator discretion, but there should be at least a 14 day window between start of cytoreductive therapy and start of daratumumab
* Blast count ˂20K/day (hydrea use is allowed)

Exclusion Criteria:

* No demonstrable evidence of donor chimerism (˂ 55% donor CD3 or CD33 chimerism)
* Patients with a molecular mutation without chromosomal abnormalities or declining chimerisms (MRD status must be verified by surface marker and mutational analyses)
* Active graft-versus-host disease (GvHD) grades II-IV; prior acute GVHD could have occurred but resolved at time of initiation of daratumumab
* Extensive chronic GvHD requiring ongoing immunosuppression with calcineurin inhibitors
* Patients with FLT3+ AML or blast crisis CML who have not yet received post-transplant TKI therapy
* Active central nervous system (CNS) disease testicular disease

EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.; seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).

* Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
* History of grade IV anaphylactic reaction to monoclonal antibody therapy
* Active autoimmune disease prior to transplant
* Concurrent use of any other investigational drugs