Oral Arsenic (ATO) in Low-risk Myelodysplastic Syndromes (MDS)
- Conditions
- Low-risk Myelodysplastic Syndromes
- Interventions
- Registration Number
- NCT06670222
- Lead Sponsor
- Groupe Francophone des Myelodysplasies
- Brief Summary
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).
- Detailed Description
Dose escalation cohort to determine the dose limiting toxicity according to a BOIN (Bayesian optimal interval) scheme.
Patients will receive one dose of study treatment (oral Arsenic (ATO)) 5d/7 for 21 days over a 28-day cycle.
Three doses of ATO will be tested (0.10 mg/kg, 0.15 mg/kg and 0.20 mg/kg), and 9 patients will be treated at each dose.
An expansion cohort at the selected dose based on DSMB recommendations will be conducted with 6 patients, for a maximum of 15 patients included at this dose level.
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.
If there is no response, patients will stop treatment and enter the follow-up phase of the study.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ATO Arsenic Trioxide (ATO) Oral Arsenic treatment
- Primary Outcome Measures
Name Time Method To determine the dose-limiting toxicity (DLT) of oral Arsenic (ATO) At the end of cycle 1 (each cycle is 28 days) 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.
- Secondary Outcome Measures
Name Time Method To determine safety profile Through study completion, an average of 2 years Toxicities measured according to CTCAE (Common Terminology Criteria for Adverse Events)
Pharmacokinetics At the end of cycle 1 (each cycle is 28 days) Measurement of the residual concentration (Cmin) of oral ATO
Efficacy At the end of cycle 3 (each cycle is 28 days) Response rate (Complete Response + Partial Response + stable disease with hematological improvement according to IWG (International Working Group) 2018 criteria)
Response duration Through study completion, an average of 2 years Response duration measured from date of objective response to date of relapse or progression (or date of last news in absence of event)
Progression-free survival Through study completion, an average of 2 years Rate and time to transformation to high-risk myelodysplastic syndrome (MDS) or Acute Myeloid Leukemia (AML)
Overall survival Through study completion, an average of 2 years Overall survival from date of inclusion to death or date of last news
Trial Locations
- Locations (3)
CHU de Nice - Hôpital l'Archet - Service d'hématologie clinique
🇫🇷Nice, France
Hôpital Saint Louis - Service Hématologie séniors
🇫🇷Paris, France
Institut Gustave Roussy - Service d'hématologie
🇫🇷Villejuif, France