ARSENIC TRIOXIDE for Myelodysplastic syndromes | Low-risk myelodysplastic syndrome

Inclusion criteria

• {"criterion_text":"- Myelodysplastic syndrome according to WHO 2022 classification"}
• {"criterion_text":"- 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 formula)"}
• {"criterion_text":"- Adequate liver function defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal"}
• {"criterion_text":"- Patient not refractory to platelet transfusions"}
• {"criterion_text":"- Diabetic patients should have well-controlled diabetes with HbA1c level ≤ 7.5% prior to inclusion"}
• {"criterion_text":"- 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: o 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 EOT. o If sexually active, agreed to have used, and been able to comply with, highly effective contraception** without interruption, 5 weeks prior to starting IP, during treatment with IP (including dose interruptions), and for 24 weeks after discontinuation of IP. **Highly effective contraception was defined in this protocol as the following (information also appeared in the ICF): 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. \tMale 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 IP discontinuation, even if he had undergone a successful vasectomy."}
• {"criterion_text":"- Patient must understand and voluntarily sign informed consent form"}
• {"criterion_text":"- Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements"}
• {"criterion_text":"- Performance status 0-2 at the time of screening"}
• {"criterion_text":"- 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 IP discontinuation, even if he had undergone a successful vasectomy."}
• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Patient with low-risk MDS according to IPSS-R classification (very low, low, intermediate): -\tnon-sideroblastic who failed to achieved a response or who subsequently relapse after ESA (at Epoetin alfa 60000UI or equivalent over at least 12 weeks) without disease progression or ineligible to ESA (defined by EPO > 500UI/L) -\tsideroblastic 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 -\tdel (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"}
• {"criterion_text":"- Transfusion dependence (at least 3 RBC required within a 16-week period and at least 2 transfusion episodes during this period)"}
• {"criterion_text":"- Patient not eligible for another clinical trial"}

Exclusion criteria

• {"criterion_text":"- Severe infection or any uncontrolled severe condition"}
• {"criterion_text":"- Active cancer or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast"}
• {"criterion_text":"- Patient already enrolled in another therapeutic trial of an investigational drug"}
• {"criterion_text":"- Known HIV infection or active hepatitis B or C"}
• {"criterion_text":"- Patients with hypoxia requiring oxygen assistance"}
• {"criterion_text":"- Patients with overrisk of encephalopathy (ie: vitamin B1 deficiency)"}
• {"criterion_text":"- Patients taking concomitant treatment known to prolong the QT interval"}
• {"criterion_text":"- Known hypersensibility to the arsenic or one excipient"}
• {"criterion_text":"- Persons not affiliated to a social security system or equivalent"}
• {"criterion_text":"- Persons deprived of liberty by judicial or administrative decision"}
• {"criterion_text":"- Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice)"}
• {"criterion_text":"- Women who are or could become pregnant or who are currently breastfeeding"}
• {"criterion_text":"- Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form"}
• {"criterion_text":"- Patient eligible for allogeneic stem cell transplantation"}
• {"criterion_text":"- Uncontrolled hypertension"}
• {"criterion_text":"- Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months"}
• {"criterion_text":"- QTcF > 460ms"}
• {"criterion_text":"- Use of investigational agents within 30 days or any anticancer therapy (including IMiD) within 2 weeks before the study entry with the exception of hydroxyurea. The patient must have recovered at least a grade 1 from all acute toxicity from any previous therapy. However, patients may have received Lenalidomide, hypomethylating agent, or anti-lymphocytic serum (ALS) (but not within 4 weeks before the study entry and, for ALS, within 16 weeks before the study entry)."}
• {"criterion_text":"- Use of EPO within 4 weeks before the study entry"}

Primary endpoints

• {"endpoint_text":"- Part 1 (Phase I study): Dose-limiting toxicity (DLT) of oral ATO over an observation period from day 28 to day 42 following the start of cycle 1","definition_or_measurement_approach":"DLT observed over an observation period from day 28 to day 42 following the start of cycle 1"}
• {"endpoint_text":"- Part II (Expansion Phase): Erythroid response rate (HI-E) after 12 weeks oral ATO treatment","definition_or_measurement_approach":"Erythroid response rate (HI-E) assessed after 12 weeks of oral ATO treatment"}

Secondary endpoints

• {"endpoint_text":"- Safety profile and tolerability measured according to CTCAE (latest version)","definition_or_measurement_approach":"Safety and tolerability assessed per CTCAE (latest version)"}
• {"endpoint_text":"- Bioequivalence compared to IV ATO in terms of PK/PD","definition_or_measurement_approach":"Pharmacokinetic/pharmacodynamic comparison versus IV ATO"}
• {"endpoint_text":"- Response to treatment will be assessed after cycle 3 according to IWG 2018 criteria","definition_or_measurement_approach":"Response assessed after cycle 3 using IWG 2018 criteria (CR, PR, stable disease with hematological improvement)"}
• {"endpoint_text":"- Response duration measured from date of objective response to date of relapse or progression (or date of last news in absence of event)","definition_or_measurement_approach":"Duration from objective response to relapse/progression or last contact"}
• {"endpoint_text":"- Rate and time to transformation to high-risk MDS or AML","definition_or_measurement_approach":"Measured as rate and time to transformation to high-risk MDS or AML"}
• {"endpoint_text":"- Progression-free survival","definition_or_measurement_approach":"PFS measured from inclusion to progression or death"}
• {"endpoint_text":"- Overall survival from date of inclusion to death or date of last news","definition_or_measurement_approach":"Overall survival measured from date of inclusion to death or last contact"}
• {"endpoint_text":"- Exploratory criteria: factors associated with survival and response, including IPSS-R, karyotype and somatic mutations (IPSS-M)","definition_or_measurement_approach":"Exploratory analyses to identify factors associated with survival/response including IPSS-R, karyotype and somatic mutations (IPSS-M)"}

France

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

14-08-2025

Processing Time Days

205

Number Of Sites

3

Number Of Participants

24

Primary sponsor

Full Name

Groupe Francophone Des Myélodysplasies

Organisation Type

Patient organisation/association

Country Of Registered Address

France