Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN

This clinical trial involves individuals who have been diagnosed with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), or MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-unclassifiable) and are planning to have an allogeneic hematopoietic stem cell transplant ("bone marrow transplant"). The goal of this research study is to (1) test the safety of adding the study drug, Venetoclax, to a standard of care conditioning regimen for bone marrow transplantation as a possible means of eliminating residual (left-over) disease prior to transplant, (2) to test the safety of combination Venetoclax and azacitidine as "maintenance therapy" after transplant to possibly prevent disease recurrence and (3) to test the safety of combination Venetoclax and oral decitabine/cedazuridine as "maintenance therapy" after transplant to possibly prevent disease recurrence. * The name of the study drug involved in this study is Venetoclax. * It is expected that about 102 people will take part in this research study.

* This research study is a Phase I clinical trial, which tests the safety of an investigational drug and tries to define the appropriate dose and schedule of the investigational drug to use for further studies. "Investigational" means that the drug is being studied. * There are four parts to this research study: * Part 1 is to determine a safe dose of the study drug, Venetoclax, when given in combination with a standard chemotherapy. Part 2 is to determine the safety of post-transplant maintenance therapy with the combination of azacitidine and venetoclax. Part 3 is to determine the safety of post-transplant maintenance therapy with the combination of oral decitabine/cedazuridine and venetoclax. Part 4 is to determine the safety of adding venetoclax to FluBu2/ post-transplant cyclophosphamide/ tacrolimus/ mycophenolate mofetil for patients undergoing RIC allo-HCT. * Participants enrolled in Part 1 of this study, will receive Venetoclax in combination with conditioning chemotherapy (prior to transplantation). * Participants enrolled in Part 2, Part 3, and Part 4 of the study, will also receive Venetoclax in combination with conditioning chemotherapy (prior to transplantation) and will have the opportunity to receive maintenance chemotherapy (after transplantation) for potentially a year. * Part 1, Part 2, and Part 3 of this research study will have a Dose-Escalation phase. The Dose-Escalation phase is the part of the study where treatment dose and schedule are being tested. * In Part 1, the Dose-Escalation phase is when venetoclax will be given at different doses until the safest maximum dose has been identified. Part 1 also includes a second phase of the study which is called the Dose-Expansion phase, during which more participants will be treated at this dose level to obtain additional information on safety. * In Part 2, the Dose-Escalation phase is where the combination of venetoclax and azacitidine will be given after transplantation at different schedules. * In Part 3, the Dose-Escalation phase is where the combination of venetoclax and oral decitabine/cedazuridine will be given after transplantation at different schedules. * For both the Dose-Escalation or Dose-Expansion phase of this study, there will be a screening period, a pre-transplant period, a transplant period, and a post-transplant follow up period. * In this research study, participants will receive venetoclax plus chemotherapy. Participants in Part 1, Part 2, Part 3, and Part 4 of this study will receive chemotherapy immediately prior to transplantation, which is called the "conditioning regimen." The conditioning regimen chemotherapy will suppress the immune system and may help to destroy cancer cells. During this process normal bone marrow cells are destroyed as well, thus making way for donor stem cells. * Fludarabine and busulfan (FluBu2) are both chemotherapies and a common conditioning regimen. * In this study, Venetoclax is added to the conditioning regimen (FluBu2) prior to transplantation to eliminate leftover blood cancer cells prior to transplant. * Participants in Part 2 and Part 4 of the study will also have the opportunity to receive venetoclax plus azacitidine after transplantation. The combination of these two drugs is called "maintenance therapy," which is treatment given after transplant to potentially reduce the chance of disease relapse. Relapse is a cause of transplant failure and can occur when there are leftover blood cancer cells. * Participants in Part 3 of the study will also have the opportunity to receive venetoclax plus oral decitabine/cedazuridine after transplantation. The combination of these two drugs is called "maintenance therapy," which is treatment given after transplant to potentially reduce the chance of disease relapse. Relapse is a cause of transplant failure and can occur when there are leftover blood cancer cells. * The FDA (U.S. Food and Drug Administration) has approved Venetoclax in combination with cytarabine, azacitidine or decitabine for the treatment of newly diagnosed acute myeloid leukemia, but not for use in with conditioning chemotherapy prior to transplantation or after transplant with maintenance chemotherapy. Venetoclax is an oral drug that selectively inhibits Bcl-2, which is critical for keeping cancer cells alive.