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

NCT06670222 | Recruiting Phase 1 DMC

• 2 other identifiers: ATOMYELO2024-515311-22-00
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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).

Conditions

Low-risk Myelodysplastic Syndromes

Keywords

Oral Arsenic; Low-risk myelodysplastic syndromes

Outcome Measures

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.

  At the end of cycle 1 (each cycle is 28 days)

Secondary Outcomes (8)

• To determine safety profile

  Through study completion, an average of 2 years

• Pharmacokinetics

  At the end of cycle 1 (each cycle is 28 days)

• Pharmacokinetics

  At the end of cycle 1 (each cycle is 28 days)

• Pharmacokinetics

  At the end of cycle 1 (each cycle is 28 days)

• Efficacy

  At the end of cycle 3 (each cycle is 28 days)

Study Arms (1)

ATO

EXPERIMENTAL

Oral Arsenic treatment

Drug: Arsenic Trioxide (ATO)

Interventions

Arsenic Trioxide (ATO) DRUG

Study 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.

ATO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Any patient meeting one of the following criteria cannot be included in the study:
• 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
• Use of investigational agents within 30 days or any anticancer therapy (including IMiD (Immunomodulatory treatments)) 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).
• Use of EPO within 4 weeks before the study entry
• 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
• Patient already enrolled in another therapeutic trial of an investigational drug
• Known Human Immunodeficiency Virus infection or active hepatitis B or C
• Women who are or could become pregnant or who are currently breastfeeding
• Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form
• Patient eligible for allogeneic stem cell transplantation
• No affiliation to a health insurance system

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead

Study Sites (3)

CHU de Nice - Hôpital l'Archet - Service d'hématologie clinique

Nice, 06200, France

NOT YET RECRUITING

Hôpital Saint Louis - Service Hématologie séniors

Paris, 75010, France

RECRUITING

Institut Gustave Roussy - Service d'hématologie

Villejuif, 94805, France

NOT YET RECRUITING

MeSH Terms

Interventions

Arsenic Trioxide

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Central Study Contacts

Thomas CLUZEAU, MD/PhD

CONTACT

+33 492035839; cluzeau.t@chu-nice.fr

Jean Baptiste MICOL, MD

CONTACT

jeanbaptiste.micol@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose escalation cohort to determine the dose limiting toxicity according to a BOIN (Bayesian optimal interval) scheme. Three doses of oral Arsenic will be tested, and 9 patients will be treated at each dose. An expansion cohort at the selected dose will be conducted with 6 patients, for a maximum of 15 patients included at this dose level.

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: November 1, 2024
• Study Start: July 22, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)