Oral Arsenic (ATO) in Low-risk Myelodysplastic Syndromes (MDS)
ConditionLow-risk Myelodysplastic Syndromes
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorGroupe Francophone des Myelodysplasies
About this trial
Phase I study with dose-escalation and expansion evaluating the safety and efficacy of oral Arsenic (ATO) in low-risk Myelodysplastic Syndromes having failed to Erythropoiesis Stimulating Agents and Luspatercept (or ineligible for the latter).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Myelodysplastic syndrome according to WHO (World Health Organization) 2022 classification
Age ≥ 18 years
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
Disqualifiers
Severe infection or any uncontrolled severe condition
Uncontrolled hypertension
Significant cardiac disease - NYHA (New York Heart Association) Class III or IV or having suffered a myocardial infarction in the last 6 months
QTcF (Fridericia's corrected QT interval) > 460ms
Trial design
Design model
Single group
Treatments tested in this trial
Arsenic Trioxide (ATO)
DrugStudy treatment: oral Arsenic 5d/7 for 21 days over a 28-day cycle, three doses tested (0.10 mg/kg, 0.15 mg/kg and 0.20 mg/kg). Dose escalation cohort to determine the dose limiting toxicity according to a BOIN (Bayesian optimal interval) scheme, 9 patients will be treated at each dose. An expansion cohort at the selected dose will be conducted with 6 patients. Tolerability will be assessed after one treatment cycle. Response will be assessed after 3 cycles of treatment. Responders may continue study treatment until progression or limiting toxicity. Limiting toxicity is defined as any grade III/IV extra-hematological toxicity or grade IV hematological toxicity lasting more than 25 days.
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: ATOExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To determine the dose-limiting toxicity (DLT) of oral Arsenic (ATO)
Dose-limiting toxicity will be defined by the occurrence during the first treatment cycle of any of the following toxicities related to the trial drug (oral ATO): * Non-hematological toxicity of grade ≥ 3 * Hematological toxicity of grade ≥ 4 corresponding to a decrease of 50% or more of absolute neutrophil count (ANC) or platelet count from baseline or lower limit (if baseline was above normal), without recovery at D42 of the first cycle.
Time frame
At the end of cycle 1 (each cycle is 28 days)Secondary outcomes
1
To determine safety profile
Toxicities measured according to CTCAE (Common Terminology Criteria for Adverse Events)
Time frame
Through study completion, an average of 2 years2
Pharmacokinetics
Measurement of the peak plasma concentration (Cmax) of oral ATO
Time frame
At the end of cycle 1 (each cycle is 28 days)3
Pharmacokinetics
Measurement of area under the plasma concentration versus time curve (AUC) for oral ATO
Time frame
At the end of cycle 1 (each cycle is 28 days)4
Pharmacokinetics
Measurement of the residual concentration (Cmin) of oral ATO
Time frame
At the end of cycle 1 (each cycle is 28 days)Sponsors and contacts
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Source ClinicalTrials.gov