Inqovi Maintenance Therapy in Myeloid Neoplasms

Inclusion Criteria:

• Pathologically confirmed diagnosis of myelodysplastic syndrome (MDS) or chronicmyelomonocytic leukemia (CMML).
• Subjects should have less than 5% myeloblasts on a bone marrow biopsy within 42days prior to the start of conditioning.
• Age ≥ 18
• Will undergo first allogeneic hematopoietic stem cell transplantation (HSCT) for theirmalignancy.
• Transplantation will be performed with the use of reduced intensity conditioning (RIC).
• HSCT Donor will be one of the following:
• 5/6 or 6/6 (HLA-A, B, DR) matched related donor
• 7/8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelatedsetting must be at the allele level.
• Haploidentical related donor, defined as ≥ 3/6 (HLA-A, B, DR) matched
• ≥ 4/6 (HLA-A, B, DR) umbilical cord blood (UCB). Matching in the UCB setting isat the antigen level. Recipients may receive either one or two UCB units. In thecase of 2 UCB units, both units must have been at least 4/6 matched with therecipient.
• ECOG performance status 0-2.
• Participants must have normal organ and function as defined below:
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 3x institutional upper limit ofnormal (ULN)
• Total bilirubin < 1.5 x ULN (with the exception of subjects with a history ofGilbert's syndrome)
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
• LVEF must be equal to or greater than 50%, as measured by MUGA scan or echocardiogram
• Female patients of childbearing potential must have a negative pregnancy test, asmeasured by serum or urine testing
• The effects of decitabine/cedazuridine on the developing human fetus are unknown. Forthis reason women of child-bearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) during theentire study treatment period and through 6 months after the last dose of treatment
• Ability to understand and the willingness to sign a written informed consent document. Eligibility Criteria Prior to Treatment (Post HCT)
• Maintenance therapy may begin at any time between day 30 and day 120 followinghematopoietic cell transplantation. Participants must meet the following criteria tobe eligible to treatment on this study:
• Chimerism studies reveal that ≥ 70% of blood or bone marrow cells, or of the CD33expressing fraction, are of donor origin.
• There is no acute graft versus host disease (GVHD), requiring an escalation ofcorticosteroid dose or addition of other agent in the 4 weeks prior to Cycle 1Day 1.
• There is no morphological evidence of relapsed/recurrent/residual disease (asassessed by post HCT bone marrow biopsy and aspirate).
• There is no systemic infection requiring IV antibiotic or antifungal or antiviraltherapy within 7 days of starting decitabine/cedazuridine
• ANC ≥ 1000/µL
• Platelets ≥ 50,000/µL
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 3x institutional upper limit ofnormal (ULN)
• Total bilirubin < 1.5 x ULN (with the exception of subjects with a history ofGilbert's syndrome)
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)

Exclusion Criteria:

• Prior allogeneic hematopoietic stem cell transplants.
• History of other malignancy(ies) unless
• the participant has been disease-free for at least 12 months and is deemed by theinvestigator to be at low risk of recurrence of that malignancy, or
• the only prior malignancy was cervical cancer in situ and/or basal cell orsquamous cell carcinoma of the skin
• Known diagnosis of active hepatitis B or hepatitis C
• Current or history of congestive heart failure New York Heart Association (NHYA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF < 50%, asmeasured by MUGA scan or echocardiogram)
• Current or history of ventricular or life-threatening arrhythmias or diagnosis oflong-QT syndrome
• Systemic uncontrolled infection
• Known dysphagia, short-gut syndrome, gastroparesis, or other condition(s) that limitsthe ingestion or gastrointestinal absorption of drugs administered orally
• Uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg)
• QTc interval (i.e., Friderica's correction [QTcF]) ≥ 450 ms or other factors thatincrease the risk of QT prolongation or arrhythmic events (e.g., heart failure,hypokalemia, family history of long QT interval syndrome) at screening
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• Breastfeeding women