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
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
The primary objective of study Part A is to assess the safety of talacotuzumab (formerly
 CSL362) monotherapy and confirm the recommended Phase 2 dose (RP2D) in participants with
 acute myeloid leukemia (AML) for whom experimental therapy is appropriate. The primary
 objective of study Part B are to assess complete response (CR) rate and overall survival (OS)
 in participants with AML who are not eligible for intense induction chemotherapy and who are
 randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone.
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