Phase 2 Study Of Imetelstat for Patient With Myelodysplastic/Myeloproliferative Neoplasms

Eligibility Criteria * Age ≥18 years as MF and CMML are very rare diseases in the pediatric population. * Diagnosis of MDS/MPN according to WHO including: 1. CMML-1 or CMML-2 with resistance or intolerance to hydroxyurea (if myeloproliferative subtype defined by WBC \>13x109/L) or with no response or intolerance to 4 cycles of azacitidine or decitabine or relapse or progression after any number of cycles. CMML-1 Participants with Hgb \<11g/dL, TSS score 20 or splenomegaly (defined as \>5cm under the lower costal margin by physical exam or \>12cm by imaging) in which hydroxyurea or HMA therapy is not indicated will also be eligible. 2. MDS/MPN with neutrophilia (previous atypical CML) or MDS/MPN-NOS with either \>5% bone marrow blasts, Hgb \<11g/dL or requiring transfusions, platelet count \>450x109/L, TSS symptom score 20 or splenomegaly \>5cm under the lower costal margin (or \>12cm by imaging). 3. MDS/MPN with SF3B1 mutation and thrombocytosis (prior MDS/MPN-RS-T) with Hgb \<11g/dL or requiring transfusions or with platelet count \>450x109/L who have no response or failure to erythroid stimulating agents or who are unlikely to benefit due to endogenous erythropoietin levels \>500mU/mL or who have intolerance or resistance to hydroxyurea. Participants having received other prior therapies including but not limited to lenalidomide, luspatercept, JAK inhibitors or HMA will also be eligible. * ECOG performance status ≤2 * Adequate hepatic function with total bilirubin \</=3 x ULN, AST or A LT \</= 3xULN unless related to disease involvement. * Serum creatinine clearance \>30mL/min and no end/stage renal disease (using Cockcroft-Gault). * Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GMCSF, Procrit, aranesp, thrombopoietin) is allowed at any time prior to cycle 1 day 1 of therapy. * Participant (or patient's legally authorized representative) must have signed an informed consent document indicating that the Participant understands the purpose of and procedures required for the study and is willing to participate in the study. Non-English-speaking Participants may be consented. * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, Participants should be class 2B or better. * Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until 30 days after last dose of imetelstat therapy. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female Participants, between the onset of menses (as early as 8 years of age) and 55 years unless the Participant presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria * Participants who are currently receiving treatment for a malignancy (not including basal cell carcinoma,nonmelanoma skin cancer, cervical carcinoma in situ, early-stage breast cancer or localized prostate cancer treated with hormone therapy). Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit or not requiring active treatment at the time of enrollment. * Participants who are receiving any other investigational agents within 7 days of C1D1 or who have received prior imetelstat therapy. * Active, uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been initiated and, at the time of screening, there is no evidence of infection worsening, such as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs, or radiographic findings attributable to infection. * Platelet count \<50x109/L prior to enrollment and treatment initiation except if related to either recent treatment for MDS/MPN or treatment with cytotoxic therapy for any other reason. * Pregnant women are excluded from this study because imetelstat has potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study. * Participants with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine devices \[IUD\], double-barrier method \[spermicidal jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) throughout the study. * Female Participants with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening. * Participants receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy within 7 days of therapy initiation. * Participants with psychiatric illness/social situations that would limit compliance with study requirements.