An Efficacy and Safety Study of Decitabine (DACOGEN) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus Decitabine (DACOGEN) Alone in Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy

This is a 2-part, open-label, multicenter, Phase 2/3 study conducted in participants with AML
who are suitable for experimental therapy (Part A) and in participants with untreated AML who
are not eligible for intense induction chemotherapy or hematopoeitic stem cell
transplantation (HSCT) (Part B). In Study Part A, the safety, pharmacokinetic (PK) and
pharmacodynamic (PD) profile will be assessed to confirm the RP2D of 9 milligram per kilogram
(mg/kg) talacotuzumab. In Study Part B, participants will be randomized in a 1:1 ratio into
either decitabine + talacotuzumab (arm 1) or decitabine alone (arm 2). Blood and bone marrow
sampling will be done in Part A and B for disease assessment, PK, PD, and biomarkers will be
collected in all participants. Safety will be monitored throughout the study.

Inclusion Criteria:

- De novo or secondary acute myeloid leukemia (AML) (post myelodysplastic syndrome [MDS]
or myeloproliferative neoplasm [MPN] or after leukemogenic chemotherapy) according to
WHO 2008 criteria

For Part A:

- Participants With AML: treatment naive or relapsed for whom experimental therapy is
appropriate (as assessed by their treating physician)

For Part B:

- Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have
at least one of the following: congestive heart failure or ejection fraction less than
or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter
(mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung
diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced
expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest
requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2;
prior or current malignancy that does not require concurrent treatment; unresolved
infection; comorbidity that, in the Investigator's opinion, makes the participant
unsuitable for intensive chemotherapy and must be documented and approved by the
Sponsor before randomization

- Previously untreated AML (except: emergency leukopheresis and/or hydroxyurea during
the screening phase to control hyperleukocytosis but must be discontinued at least one
day prior to start of study therapy)

- Not eligible for an allogeneic hematopoietic stem cell transplantation

- ECOG Performance Status score of 0, 1 or 2

- A woman must be either: Not of childbearing potential: postmenopausal (more than [>]
45 years of age with amenorrhea for at least 12 months; If, of childbearing potential
must be practicing a highly effective method of birth control

- A woman of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening

- 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 for at least
3 months after last study treatment

Exclusion Criteria:

- Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARalpha)

- For Part B only: Known leukemic involvement or clinical symptoms of leukemic
involvement of the central nervous system

- Participants who received prior treatment with a hypomethylating agent

- For Part A only: Participants who did not recover from all clinically significant
toxicities (excluding alopecia and hematologic toxicities) of any previous surgery,
radiotherapy, targeted therapy, or chemotherapy to less than or equal to Grade 1

- Any uncontrolled active systemic infection that requires treatment with intravenous
(IV) antibiotics

- A history of human immunodeficiency virus (HIV) antibody positive or tests positive
for HIV if tested at screening

- Active systemic hepatitis infection requiring treatment or other clinically active
liver disease