Oral Arsenic (ATO) in Low-risk Myelodysplastic Syndromes (MDS)

Inclusion Criteria22

• Patients must meet all the following criteria to participate in the study:
• Myelodysplastic syndrome according to WHO (World Health Organization) 2022 classification
• Age ≥ 18 years
• Patient with low-risk Myelodysplastic Syndromes according to Revised International Prognostic Scoring System (IPSS-R) classification (very low, low, intermediate):
• non-sideroblastic who failed to achieved a response or who subsequently relapse after Erythropoiesis Stimulating Agents (ESA) (at Epoetin alfa 60000UI or equivalent over at least 12 weeks) without disease progression or ineligible to ESA (defined by Erythopoietine (EPO) > 500UI/L)
• sideroblastic who failed to achieved a response or who subsequently relapse after ESA (at Epoetin alfa 60000UI or equivalent over at least 12 weeks) or ineligible for ESA (defined by EPO >500UI/L) and who failed to achieved a response or who subsequently relapse after Luspatercept
• del (5q) who failed to achieved a response or who subsequently relapse after ESA (at Epoetin alfa 60000IU or equivalent over at least 12 weeks) and who failed to achieved a response or who subsequently relapse after Lenalidomide
• Transfusion dependence (at least 3 RBC (Red Blood Cell) within a 16-week period and at least 2 transfusion episodes during this period)
• Patient not eligible for another clinical trial
• Adequate renal function defined by creatinine level less than 1.5 times the upper limit of normal and creatinine clearance ≥ 40mL/min (according to MDRD (Modification of Diet in Renal Disease) formula)
• Adequate liver function defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal
• Patient not refractory to platelet transfusions
• Written consent
• Patient must understand and voluntarily sign informed consent form
• Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements
• Performance status 0-2 at the time of screening
• A FCBP (female of childbearing potential) for this study was defined as a sexually mature woman who: (1) had not undergone a hysterectomy or bilateral oophorectomy; or (2) had not been naturally postmenopausal (amenorrhea following cancer therapy did not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
• A FCBP participating in the study must:
• Have had 2 negative pregnancy tests as verified by the investigator prior to starting IP (unless the screening pregnancy test was done within 72 hours of Cycle 1 Day 1). She must have had agreed to ongoing a monthly pregnancy testing during the course of the study and after end of treatment.
• If sexually active, agreed to have used, and been able to comply with, highly effective contraception** without interruption, 5 weeks prior to starting treatment, during treatment (including dose interruptions), and for 24 weeks after discontinuation of treatment.
• Highly effective contraception was defined in this protocol as the following (information also appeared in the Informed Consent Form): Hormonal contraception (eg, birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation (tying your tubes), or a partner with a vasectomy.
• Male subjects must: Have agreed to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane), during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions, and for at least 24 weeks following treatment discontinuation, even if he had undergone a successful vasectomy.