Open Label 2-Arm Study of Venetoclax in Combination with Azacitidine Versus Best Supportive Care after Allogeneic Stem Cell Transplantation in Subjects with Acute Myeloid Leukemia (AML)

Prior treatment

• Subjects with favorable cytogenetic risk per NCCN 2016 criteria and in first complete remission prior to transplant are not eligible to enroll in this study.

Other illness

• History of disease progression during prior treatment with venetoclax.
• History of any other malignancy within 2 years prior to study entry, except for: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; Myelodysplastic Syndrome; Myeloproliferative neoplasm (only allowed if it transformed to AML and AML should be the indication for marrow transplantation).
• Known infection with HIV or subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV) with high viral titers.

Lab values

• Presence of clinical or laboratory symptoms/signs of extramedullary myeloid malignancy.

• Adult male or female ≥18 years old for Part 1 and, male or female at least 12 years old for Part 2.
• (Notes a - b): a) C1D1 must occur within 28 to 100 days of this subsequent transplant date. b) If there is a subsequent (second) graft failure after reconsent during the registration period, the subject will not be permitted to enroll into the study.
• No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Subject must be diagnosed with AML by World Health Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell transplantation or have received allogeneic stem cell transplantation within the past 60 days.
• Blast percentage in bone marrow prior to pre-transplant conditioning must be < 10%. Blast count in peripheral blood must be "0" and malignant Blast percentage in bone marrow must be < 5% after transplant within 7 days prior to Cycle 1 Day 1.
• Bilirubin ≤3 × ULN* within 7 days prior to Cycle 1 Day 1. For Part 1: ANC ≥1,500/µL, measured twice at least 2 days apart (approximately 48 hours) and within 1 week prior to Cycle 1 Day 1. Subjects should not have granulocyte-colony stimulating factor (G-CSF) treatment for 7 days before first ANC count. For Part 2: ANC ≥1,000/µL, measured twice at least 2 days apart (approximately 48 hours) and within 1 week prior to Cycle 1 Day 1 or prior to dosing on Cycle 1 Day 1. Subjects should not have granulocyte- colony stimulating factor (G-CSF) treatment for 7 days before first ANC count.
• Part 1: Platelet count ≥80,000/µL measured twice at least 2 days apart (approximately 48 hours) and within 1 week prior to Cycle 1 Day 1. Subjects should not have supportive treatment (e.g., transfusions and/or growth factors) for 7 days before first platelet count. Part 2: Platelet count ≥50,000/µL measured twice at least 2 days apart (approximately 48 hours) and within 1 week prior to Cycle 1 Day 1 or prior to dosing on Cycle 1 Day 1. Subjects should not have supportive treatment (e.g., transfusions and/or growth factors) for 7 days before first platelet count.
• Adequate renal function as demonstrated by a creatinine clearance > 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24- hour urine collection.
• Subjects ≥17 years old must have a Karnofsky Performance Scale (KPS) score > 50 and Subjects 12 to 16 years old must have a Lansky Play- Performance Scale (LPPS) score > 40. Part 2: If a subject is 12 to 16 at the time of screening and turns 17 during the study, the subject will continue with the LPPS.
• Cycle 1 Day 1 administration of 1st dose of the study drug(s) must occur within 28 to 100 days after transplant. Subjects may enter into Screening upon the first instance of meeting the count recovery criteria without the need for supportive care (e.g., growth factors and/or platelet transfusions) for at least 7 days prior. Upon entering screening, subjects must maintain count thresholds on at least 2 occasions (approximately 48 hours apart) in the absence of supportive care (platelet transfusion/G-CSF within 7 days).
• If graft failure occurs during the registration period and a subsequent transplant is planned, the subject can be reconsented for the study.