PRIMARY OBJECTIVES:

      I. To evaluate safety and tolerability of daratumumab and escalating doses of donor
      lymphocyte infusions (DLI) in post-hematopoietic cell transplantation (HCT) patients with
      relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed to AML
      (phase I).

      II. To evaluate overall response rate to daratumumab and DLI in patients with post-HCT
      relapsed AML and MDS (phase II).

      SECONDARY OBJECTIVES:

      I. To assess overall response rates in minimal residual disease (MRD) positive patients and
      in patients with overt morphological relapse.

      II. To assess MRD conversion rates from MRD positive to MRD negative. III. To determine the
      post-relapse 6-month overall response (OS) rates of patients with relapsed AML and MDS
      following allogeneic hematopoietic stem cell transplantation (allo-HSCT) who are treated with
      daratumumab.

      IV. To determine the rates of graft-versus-host disease (GVHD) (both grades II-IV and III-IV)
      and autoimmune side effects of daratumumab.

      V. To determine the post-relapse 6-month progression-free survival (PFS) rates of patients
      with relapsed AML and MDS following allo-HSCT who are treated with daratumumab.

      EXPLORATORY OBJECTIVES:

      I. To compare CD38 expression levels in myeloid blasts and interferon gamma (IFN-y) levels in
      plasma at the time of relapse before starting daratumumab and at progression or relapse after
      daratumumab.

      II. To compare peripheral blood T cell number and subsets (CD3, CD4, CD8, (CD38 expression on
      regulatory T cells [T-regs], CD4 and CD8), T regs, B-regulatory cells, natural killer (NK)
      cell numbers and bone marrow T cell subsets at the time of relapse before starting
      daratumumab, at the time of partial/complete response to daratumumab, and at the time of
      progression or relapse after daratumumab.

      III. To evaluate whether daratumumab has (i) direct anti-leukemia effects (ii)
      antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis
      (ADCP) and (III) immune modulation of autologous immune system (NK cells, T cells, T-regs,
      B-regulatory cells [B-regs], and myeloid-derived suppressor cells [MDSCS]) in AML.

      IV. To evaluate the effect of daratumumab on exosome content and clearance along with other
      soluble factors in AML.

      V. To evaluate serum interferon (IFN) levels pre-daratumumab, during and post-daratumumab.

      VI. To evaluate whether fratricide occurs in patients treated with daratumumab.

      OUTLINE: This is a phase I, dose escalation study of donor lymphocyte infusions followed by a
      phase II study.

      Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte
      infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity.
      Participants found to be in complete response (CR) at the end of 8 weeks may receive
      daratumumab IV once every 2 weeks for 8 weeks, and then once monthly for 6 months in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up for 1 year.