A Multi-Site Break Through Cancer Pilot Study Testing the Feasibility and Safety of Therapeutic Intervention for Patients With High-risk Clonal Cytopenia of Undetermined Significance (CCUS)

Inclusion Criteria: * Age ≥18 years. * Unexplained cytopenia(s) for at least 4 months (at least two separate labs within 4 months including at time of screening must meet this criteria). Cytopenia(s) defined as the presence of ≥ 1 of the following: * Hemoglobin (Hgb) \<12 g/dL for women and \<13g/dL for men * Absolute neutrophil count (ANC) \< 1.8 × 109/L\* * Platelet count (Plt) \<150 × 109/L \*Patients known to have a Duffy-null genotype must have anemia (Hgb \< 12g/dL for women, Hgb \<13g/dL for men) and/or thrombocytopenia (Plt \< 150 × 109/L) to be eligible for this study. * 1 pathogenic variant detected in any myeloid driver gene with a VAF of at least 0.02 (2%) identified by local next generation sequencing (NGS) of peripheral blood or bone marrow sample within 3 months from screening bone marrow biopsy. * Participants must have a high risk score per the Clonal Hematopoiesis Risk Calculator (CHRS). See APPENDIX C for calculation. * Screening bone marrow biopsy must not be diagnostic of any overt hematologic malignancy by morphologic assessment and must be consistent with a diagnosis of clonal cytopenia of unknown significance (CCUS) as determined by multi-institutional hematopathology review. * ECOG performance status 0-2 (see Appendix A). * Participants must meet the following organ function as defined below: * Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3x upper limit of normal (ULN). * Serum total bilirubin \<1.5x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis or Gilbert's syndrome. In these cases, approval from the study Sponsor-Investigator is required. * Creatinine clearance greater than 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation. * Ability to understand and the willingness to sign a written informed consent document. * For participants of the early pharmacologic intervention cohort: women of childbearing potential must use highly effective contraception during treatment for at least 6 months after the last dose and males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose. Exclusion Criteria: * Concurrent primary malignancy requiring active cytotoxic chemotherapy and/or ionizing radiation therapy. * Known inherited bone marrow failure disorder and/or germline predisposition to hematologic malignancy. * Receipt of anti-cancer therapy including any cytotoxic chemotherapy, ionizing radiation therapy, immunomodulatory agents such as lenalidomide, and targeted anti-cancer therapies including PARP inhibitors within the last 6 months. Patients with complete surgical resection of a tumor are not excluded from this study. * Anti-cancer therapy, including any cytotoxic chemotherapy, ionizing radiation therapy, immunomodulatory agents such as lenalidomide and targeted agents such as PARP inhibitors, planned in the next 6 months. Patients on hormonal adjuvant therapy for nonmetastatic breast and prostate cancer or other minimally-myelosuppressive maintenance therapies for non-metastatic cancer may be eligible at the discretion of the study PI. * Diagnosis of MDS, MPN, CMML, AML or any other hematolymphoid malignancy in the patient's lifetime. This includes individuals with MDS-defining chromosomal abnormalities identified via conventional karyotype or FISH. * Presence of a concurrent hematologic malignancy precursor state, such as smoldering multiple myeloma (SMM), and smoldering Waldenstrom's macroglobulinemia. * Presence of an early-stage hematologic precursor state-such as monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B cell lymphocytosis (MBL). * Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment). * Recent (within 3 months) vaccination with any live attenuated vaccine or vaccination with live attenuated vaccine planned during the next 15 months. \*Live attenuated vaccines include measles, mumps, rubella (MMR combined vaccine), rotavirus, smallpox, chickenpox, and yellow fever. * Laboratory evidence indicative of clinically significant red cell hemolysis. * Hypersplenism and/or evidence of portal hypertension on physical exam or imaging. * Pregnant or lactating.