Comparing 6 approaches for myelodysplastic syndromes

Exclusion

• −Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
• −Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
• −Has a known or suspected hypersensitivity to cedazuridine, azacitidine, venetoclax, or any of their excipients.
• −Has known human immunodeficiency virus (HIV) infection.
• −Is known to be positive for Hepatitis B or C infection.
• −Has known human immunodeficiency virus (HIV) infection.
• −Is known to be positive for Hepatitis B or C infection.
• −All Monotherapy Phases:
• −Has an active uncontrolled gastric or duodenal ulcer.
• −Has poor medical risk because of other conditions.
• −Has a life-threatening illness.
• −Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
• −Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
• −Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
• −Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocolProtocolThe detailed plan a study must follow.Read more →-defined first dose of study treatment, or ongoing clinically significant adverse eventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → from previous treatment with investigational drug or therapy.
• −Cannot discontinue treatment with any drugs that delay gastric emptying such as glucagon-like peptide-1 (GLP-1) and/or gastric inhibitory polypeptide (GIP) agonists in Cycles 1 and 2 of the study.
• −Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more → and Phase 2Phase 2A middle-stage study looking at what a treatment does and watching for side effects.Read more → Combination Therapy:
• −Has a history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
• −Has the following karyotype abnormalities: t(15;17) or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy \[t(8;21) and inv(16) are excluded in Phase 2 only\].
• −Has known active central nervous system involvement from AML.
• −Has severe hepatic impairment
• −Has severe renal impairment
• −Has a malabsorption syndrome or other condition that precludes enteral route of administration.
• −Has a cardiovascular disability status of New York Heart Association Class \>2.
• −Has significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease; or any other medical condition that in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → would adversely affect his/her participation in this study.
• −Has clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
• −Has a history of other malignancies prior to study entry with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or adequately treated and controlled with other modalities); and any early stage malignancy for which no definitive therapy is required.
• −Has a WBC count \>25,000/ microliters (μL) (hydroxyurea treatment is permitted to meet this criterion).
• −Has received treatment with any of the following:
• −A hypomethylating agent (azacitidine or decitabine) or venetoclax, including prior treatment for MDS.
• −Chimeric Antigen Receptor (CAR)-T cell therapy.
• −Investigational therapies for MDS or AML.
• −Cannot discontinue treatment with any of the following:
• −Prophylactic antifungal therapy with CYP3A inhibitor activity or other concomitant medications with moderate or strong CYP3A inhibitor activity ≥7 days or 5 halflives, whichever is greater, prior to Cycle 1 Day 1 (C1D1).
• −Drugs that are strong CYP3A or P-gp inhibitors ≥7 days or 5 half-lives, whichever is greater, prior to C1D1.
• −Cannot avoid concomitant drugs known as moderate or strong CYP3A inducers.
• −Cannot discontinue treatment with any drugs that delay gastric emptying such as GLP-1 and/or GIP agonists in Cycles 1 and 2 of the study.
• −Is participating in another research study requiring interventions such as drug therapy or study procedures.
• −Has known significant mental illness or other conditions such as alcohol or other substance abuse or addictions
• −Consumes grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit ≤7 days prior to C1D1.