Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome
Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome
Myelodysplastic Syndrome (MDS) is a group of disorders that gradually affect the ability of a
 person's bone marrow (semi-liquid tissue present in many bones like backbones) to produce
 normal blood cells. Some people with MDS have a risk of the disease progressing to acute
 myeloid leukemia (AML), and a risk of death from the disease itself. Symptoms of MDS include
 fatigue, shortness of breath, unusual paleness due to anemia (low red blood cell count), easy
 or unusual bruising, and red spots just beneath the skin caused by bleeding. The purpose of
 this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are
 when compared to AZA and a placebo (contains no medicine), in participants with newly
 diagnosed higher-risk MDS.

 Venetoclax is an investigational drug being developed for the treatment of MDS. The study
 consists of two treatment arms - In one arm, participants will receive venetoclax and AZA. In
 another arm, participants will receive AZA and placebo. Adult participants with newly
 diagnosed higher-risk MDS will be enrolled. Around 500 participants will be enrolled in
 approximately 200 sites worldwide.

 Participants in one arm will receive oral doses of venetoclax tablet and intravenous
 (infusion in the vein) or subcutaneous (given under the skin) AZA solution. Participants in
 another arm will receive oral doses of placebo tablet and intravenous or subcutaneous AZA
 solution.

 There may be higher treatment burden for participants in this trial compared to their
 standard of care. Participants will attend regular visits during the course of the study at a
 hospital or clinic. The effect of the treatment will be checked by medical assessments, blood
 and bone marrow tests, checking for side effects, and completing questionnaires.
Inclusion Criteria:

 -  Participants with a diagnosis of Myelodysplastic Syndrome (MDS) according to the 2016
 World Health Organization (WHO) classification wtih presence of < 20% bone marrow
 blasts per marrow biopsy/aspirate at screening.

 -  Participants must meet the following disease activity criteria:

 -  Overall Revised International Prognostic Scoring System (IPSS-R) score > 3
 (intermediate, high or very high).

 -  Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.

 -  Hematopoietic stem cell transplant (HSCT) eligible with no pre-arranged HSCT at
 the time of Study Day 1, or HSCT ineligible without plan for HSCT at the time of
 Study Day 1.

 Exclusion Criteria:

 -  Prior therapy for MDS with any hypomethylating agent, chemotherapy, or allogenic stem
 cell transplantation.

 -  Prior diagnosis of therapy-related MDS (t-MDS), MDS evolving from a pre-existing
 myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia
 (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia
 (JMML) and unclassifiable MDS/MPN.