Safety of SP-420 in the Treatment of Transfusional Iron Overload

Inclusion Criteria: 1. Age ≥18 2. Diagnosis of MDS or MF with transfusional iron overload 3. Patients with MDS, will include only those with MDS Revised international prognostic scoring system (IPSS-R) risk group of intermediate, high, or very high. 4. Patients with MF, will include only those with Dynamic International Prognostic Scoring System-Plus (DIPSS=Plus) risk category of intermediate-1, intermediate-2, and high risk. 5. Patients with sickle cell disease and transfusional iron overload 6. Not appropriate for other iron chelation therapy, per physician 7. Received 10 or more units of packed red blood cells in the preceding 24 months and remains red cell transfusion dependent 8. ECOG ≤ 3 9. ALT ≤ 3 times the upper limit of the normal range 10. Estimate glomerular filtration rate calculated using Cockroft Gault of ≥ 60 mL/min/1.73m2 11. Serum ferritin ≥1000 ng/ml 12. Willing to comply with all study procedures and be available for the duration of the study 13. Able to take oral medication and be willing to adhere to study medication for 28 days 14. Female patient must be post-menopausal (no menses for \> 12 consecutive months) or surgically sterile (i.e., bilateral oophorectomy, hysterectomy, or tubal sterilization; must agree to completely abstain for heterosexual intercourse; or, if sexually active, must agree to use 1 of the following methods for birth control from the date she signs the consent form until 30 days after final dose of the study drug. * Progesterone implant * Intrauterine device * Combination of 2 highly effective birth control methods (e.g., diaphragm/or cervical cap with spermicide plus a condom, hormonal contraception plus a barrier method, partner with vasectomy conducted \>60 days before screening visit plus a hormone or barrier method 15. Male patients must agree to use 1 of the following methods for birth control from the date he signs the consent form until 30 days after final dose of the study drug: be surgically sterile by vasectomy conducted \> 60 days before screening visit plus use a barrier method, or, must agree to completely abstain from heterosexual intercourse, or must agree to use a combination of 2 highly effective birth control methods (e.g., diaphragm/or cervical cap with spermicide plus a condom, hormonal contraception plus a barrier method), or have a post-menopausal partner plus barrier method. Exclusion Criteria: 1. History of kidney disease including the renal Fanconi syndrome 2. Proteinuria on urine dipstick greater than trace positive 3. Pregnant, intending to become pregnant during the study, or breastfeeding 4. Receiving another investigational drug within 30 days or 3 half-lives of the discontinued investigational agent, whichever is greater, of signing consent 5. History of significant hepatic impairment, defined by Child-Pugh class C 6. Active hepatitis B or C disease, evidenced by positive viral PCR 7. Symptomatic heart failure 8. Receiving active cytotoxic chemotherapy or radiation therapy for a second malignancy (hormonal therapy or topical therapy for squamous cell/basal cell cutaneous tumors are allowed). Treatment of the underlying hematologic malignancy with azacytidine, decitabine, venetoclax, lenalidomide, or ruxolitinib is permitted. Treatment with the supportive care agents luspatercept or erythropoietin agonists is permitted. 9. Concurrent treatment with Exjade/Jadenu (deferasirox), Desferal (deferoxamine), or Ferriprox (deferiprone) are not permitted. Patients are allowed to stop these chelators and participate in this trial 14 days after discontinuation of the other chelator.