LUSPATERCEPT for Myelodysplastic syndrome, low-risk, non-sideroblastic (LR-MDS without ring sideroblasts)

Inclusion criteria

• {"criterion_text":"- Myelodysplastic syndrome according to current WHO classification\n- Patient must understand and voluntarily sign consent form\n- Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements\n- ECOG performance status 0-2 at the time of screening\n- 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: a) 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 b) 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 12 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 12 weeks following IP discontinuation, even if he had undergone a successful vasectomy.\n- Age ≥ 18 years\n- Patients with lower risk MDS according to IPSS classification (LOW, INT-1) without RS who failed to achieved a response or who subsequently relapse after ESA (at least 60000 U EPO-a over at least 12weeks or equivalent), without disease progression (or ineligible to ESA defined by EPO > 500 UI/l)\n- Hemogobin < 9 gr/dl or Transfusion dependant (at least 3 RBCs in 16 wk in at least 2 transfusion episodes)\n- Non del(5q) syndrome\n- Adequat renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance ≥ 40 mL/min (MDRD formula)\n- Adequat liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal\n- Patient is not known to be refractory to platelet transfusions\n- Written informed consent"}

Exclusion criteria

• {"criterion_text":"- Severe infection or any other uncontrolled severe condition\n- Women who are or could become pregnant or who are currently breastfeeding\n- Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form\n- Patient eligible for allogeneic stem cell transplantation\n- Known allergies to luspatercept or EPO or any of its excipients\n- No affiliation to a health insurance system\n- Uncontrolled hypertension\n- Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months\n- del(5q) syndrome\n- 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.\n- Use of EPO within 4 weeks before the study entry\n- 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\n- Patient already enrolled in another therapeutic trial of an investigational drug\n- Known HIV infection or active hepatitis B or C"}

Primary endpoints

• {"endpoint_text":"- Part A : The dose finding study aims at determining the optimal dose (OD) that is both tolerable and has an indication of therapeutic benefit for those patients. It will use both toxicity and efficacy binary outcomes: Dose limiting toxicity (DLT), with an observation period up to day 42 of cycle 1 ; Efficacy: Treatment response will be defined at day 21 of cycle 1 by an increase in hemoglobin level of 1.5 g/dl or above.","definition_or_measurement_approach":"DLT observed with an observation period up to Day 42 of Cycle 1; efficacy defined at Day 21 of Cycle 1 by an increase in hemoglobin level of ≥ 1.5 g/dL."}
• {"endpoint_text":"- Part B: Erythroide response (HI-E) according to IWG2018 criteria at week 25 following randomization","definition_or_measurement_approach":"Erythroid response assessed according to IWG2018 criteria at Week 25 after randomization."}

Secondary endpoints

• {"endpoint_text":"- Duration of response","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free-survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

07-08-2024

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

595

Number Of Sites

35

Number Of Participants

150

Italy

Earliest CTIS Part Ii Submission Date

05-12-2025

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

18

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

Groupe Francophone Des Myelodysplasies

Organisation Type

Patient organisation/association

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"BMS","duties_or_roles":"Monetary support","organisation_type":""}