Oral arsenic (ATO) in low-risk myelodysplastic syndromes (MDS) failing Erythropoiesis Stimulating Agents and Luspatercept

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Francophone Des Myelodysplasies

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

22 Jul 2025 → ongoing

Decision date (initial)

2025-02-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Institut Gustave Roussy (IGR)

External identifiers

EU CT number

2024-515311-22-00

ClinicalTrials.gov

NCT06670222

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Therapy

Part 1 (Phase I study): To determine the dose-limiting toxicity (DLT) of oral ATO
Part 2 (Expansion phase): To determine the erythroid response rate (HI-E) after 12 weeks oral ATO treatment

Secondary objectives 8

1. To determine safety profile and tolerability measured according to CTCAE (latest version)
2. Pharmacokinetics: PK/PD
3. To determine response rate (CR + PR + stable disease with hematological improvement according to IWG 2018 criteria)
4. To determine response duration up to progression and loss of transfusion independence in responders patients
5. To determine the rate and time to transformation to high-risk MDS or AML
6. To determine progression-free survival
7. To determine overall survival
8. Exploratory study: Identify factors associated with survival and response, including IPSS-R, karyotype and somatic mutations (IPSS-M)

Conditions and MedDRA coding

low-risk Myelodysplastic Syndromes failing Erythropoiesis Stimulating Agents and Luspatercept (or ineligible for the latter)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Myelodysplastic syndrome according to WHO 2022 classification
2. Patient must understand and voluntarily sign informed consent form
3. Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements
4. Performance status 0-2 at the time of screening
5. 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.
6. Age ≥ 18 years
7. Patient with low-risk MDS according to IPSS-R classification (very low, low, intermediate): - non-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) - 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
8. Transfusion dependence (at least 3 RBC required within a 16-week period and at least 2 transfusion episodes during this period)
9. Patient not eligible for another clinical trial
10. 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)
11. Adequate liver function defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal
12. Patient not refractory to platelet transfusions
13. Diabetic patients should have well-controlled diabetes with HbA1c level ≤ 7.5% prior to inclusion
14. 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. 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.

Exclusion criteria 19

1. Severe infection or any uncontrolled severe condition
2. Women who are or could become pregnant or who are currently breastfeeding
3. Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form
4. Patient eligible for allogeneic stem cell transplantation
5. Uncontrolled hypertension
6. Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months
7. QTcF > 460ms
8. 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).
9. Use of EPO within 4 weeks before the study entry
10. 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
11. Patient already enrolled in another therapeutic trial of an investigational drug
12. Known HIV infection or active hepatitis B or C
13. Patients with hypoxia requiring oxygen assistance
14. Patients with overrisk of encephalopathy (ie: vitamin B1 deficiency)
15. Patients taking concomitant treatment known to prolong the QT interval
16. Known hypersensibility to the arsenic or one excipient
17. Persons not affiliated to a social security system or equivalent
18. Persons deprived of liberty by judicial or administrative decision
19. Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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
2. Part II (Expansion Phase): Erythroid response rate (HI-E) after 12 weeks oral ATO treatment

Secondary endpoints 8

1. Safety profile and tolerability measured according to CTCAE (latest version)
2. Bioequivalence compared to IV ATO in terms of PK/PD
3. Response to treatment will be assessed after cycle 3 according to IWG 2018 criteria
4. Response duration measured from date of objective response to date of relapse or progression (or date of last news in absence of event)
5. Rate and time to transformation to high-risk MDS or AML
6. Progression-free survival
7. Overall survival from date of inclusion to death or date of last news
8. Exploratory criteria: factors associated with survival and response, including IPSS-R, karyotype and somatic mutations (IPSS-M)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Francophone Des Myelodysplasies

Sponsor organisation

Groupe Francophone Des Myelodysplasies

Address

Opital St Louis Hemato Seniors T4, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Scientific contact point

Organisation

Groupe Francophone Des Myelodysplasies

Contact name

Thomas CLUZEAU

Public contact point

Organisation

Groupe Francophone Des Myelodysplasies

Contact name

Thomas CLUZEAU

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications