Plasmatic Biomarkers Associated With Short-term Luspatercept Treatment of Lower Risk Myelodysplastic Syndromes (MDS) Patients

NCT07830004 | Not Yet Recruiting Phase 4

• 1 other identifier: 38RC25.0319
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

Our project aims to identify metabolites and biomarkers associated with luspatercept-related asthenia in a prospective French study of low-risk MDS patients treated per EMA guidelines. This is a prospective cohort of patients with MDS treated with luspatercept. The main comparisons will consist in exploring differences in biomarkers plasma levels between patients experiencing fatigue after luspatercept initiation, vs those who do not.

Conditions

Myelodysplasia

Keywords

fatigue evaluation under LUSPATERCEPT

Outcome Measures

Primary Outcomes (1)

• metabolites and biomarkers associated with luspatercept-related asthenia

  Plasma biomarkers, including metabolites (energy metabolism, amino acids, lipid mediators), cortisol, iron-metabolism markers, serotonin, inflammatory cytokines, and selected exosomes derived microRNAs, will be explored, and associated with asthenia evaluated using CTCAE v 6.0. and PROs within the first 6 months of treatment with luspatercept. Fatigue will be graded as follows: * Grade 1: fatigue relieved by rest, * Grade 2: fatigue not relieved by rest, limiting instrumental ADL (activities of daily living) * Grade 3: fatigue not relieved by rest, limiting self-care ADL

  6 months of treatement

Secondary Outcomes (5)

• Evolution of fatigue between luspatercept initiation and up to 6 months

  baseline, Week6, Week12, Week18, Week24

• Metabolites and plasma biomarkers associated with response to luspatercept

  V0 to V 4 (Week0, Week6, Week12, Week24 except Month 4.5)

• CTCAE fatigue grading

  baseline, Week6, Week12, Week18, Week24 and weekly by chatbot up to 24 weeks

• Satisfaction questionnaire about the chatbot

  Weekly and at the end of the trial up to 24 weeks

• AE and grading according to CTCAE

  baseline, Week6, Week12, Week18, Week24

Study Arms (1)

LUSPATERCEPT

OTHER

Drug: Luspatercept

Interventions

Luspatercept DRUG

The main comparisons will consist in exploring differences in biomarkers plasma levels between patients experiencing fatigue after luspatercept initiation, vs those who do not.

LUSPATERCEPT

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent
• Participants must be ≥ 18 years of age
• Type of Participant and Target Disease Characteristics:
• Participant had documented diagnosis of MDS according to World Health Organization (WHO 2022) classification
• IPSS-R : very low, low, or intermediate-risk disease
• Less than 5% blasts (\< 5%) (in bone marrow and \< 1% PB blasts)
• Performance status: Eastern (ECOG) score of 0, 1, or 2
• Anemic patients with Hb ≤10g/dL
• First line therapy by luspatercept for lower risk MDS RS+ and MDS-RS- patients
• Or Second line therapy by luspatercept for MDS-RS+ refractory or intolerant to prior ESA treatment, as defined by any one of the following:
• Refractory to prior ESA treatment: documentation of nonresponse or response that was no longer maintained to prior ESA-containing regimen, either as a single agent or in combination (eg, with G-CSF).
• Intolerant to prior ESA treatment: Documentation of discontinuation of prior ESA-containing regimen, either as a single agent or in combination (eg, with G-CSF), at any time after introduction due to intolerance or an AE
• Patient or his entourage having a smartphone to load the application for Fidelio ( the chatbot)
• Affiliated to SS
• Higher risk MDS, del 5q syndrome, MDS-RS-T, MD- CMML

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Related Publications (8)

• Mathieu M, Friedrich C, Ducrot N, Zannoni J, Sylvie T, Jerraya N, Rousseaux S, Chuffart F, Kosmider O, Karim Z, Park S. Luspatercept (RAP-536) modulates oxidative stress without affecting mutation burden in myelodysplastic syndromes. Ann Hematol. 2022 Dec;101(12):2633-2643. doi: 10.1007/s00277-022-04993-7. Epub 2022 Oct 5.

  PMID: 36195681 BACKGROUND

• Meunier M, Guttin A, Ancelet S, Laurin D, Zannoni J, Lefebvre C, Tondeur S, Persoons V, Pezet M, Pernet-Gallay K, Chuffart F, Rousseaux S, Testard Q, Thevenon J, Jouzier C, Deleuze JF, Laulagnier K, Sadoul R, Chatellard C, Hainaut P, Polack B, Cahn JY, Issartel JP, Park S. Extracellular vesicles from myelodysplastic mesenchymal stromal cells induce DNA damage and mutagenesis of hematopoietic stem cells through miRNA transfer. Leukemia. 2020 Aug;34(8):2249-2253. doi: 10.1038/s41375-020-0738-8. Epub 2020 Feb 12. No abstract available.

  PMID: 32051530 BACKGROUND

• Jouzier C, Cherait A, Cony-Makhoul P, Hamel JF, Veloso M, Thepot S, Cluzeau T, Stamatoullas A, Garnier A, Guerci-Bresler A, Dimicoli-Salazar S, Pica GM, Cheze S, Santana C, Chermat F, Fenaux P, Park S. Red blood cell transfusion burden in myelodysplastic syndromes (MDS) with ring Sideroblasts (RS): A retrospective multicenter study by the Groupe Francophone des Myelodysplasies (GFM). Transfusion. 2022 May;62(5):961-973. doi: 10.1111/trf.16884. Epub 2022 Apr 22.

  PMID: 35452143 BACKGROUND

• Raskovalova T, Jacob MC, Park S. Myelodysplastic Syndromes. N Engl J Med. 2020 Dec 24;383(26):2590. doi: 10.1056/NEJMc2032391. No abstract available.

  PMID: 33369362 BACKGROUND

• Kaphan E, Laurin D, Lafeuillade B, Drillat P, Park S. Impact of transfusion on survival in patients with myelodysplastic syndromes: Current knowledge, new insights and transfusion clinical practice. Blood Rev. 2020 May;41:100649. doi: 10.1016/j.blre.2019.100649. Epub 2019 Dec 18.

  PMID: 31918886 BACKGROUND

• Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.

  PMID: 31914241 BACKGROUND

• Park S, Kosmider O, Maloisel F, Drenou B, Chapuis N, Lefebvre T, Karim Z, Puy H, Alary AS, Ducamp S, Verdier F, Bouilloux C, Rousseau A, Jacob MC, Debliquis A, Charpentier A, Gyan E, Anglaret B, Leyronnas C, Corm S, Slama B, Cheze S, Laribi K, Ame S, Rose C, Lachenal F, Toma A, Pica GM, Carre M, Garban F, Mariette C, Cahn JY, Meunier M, Herault O, Fenaux P, Wagner-Ballon O, Bardet V, Dreyfus F, Fontenay M. Dyserythropoiesis evaluated by the RED score and hepcidin:ferritin ratio predicts response to erythropoietin in lower-risk myelodysplastic syndromes. Haematologica. 2019 Mar;104(3):497-504. doi: 10.3324/haematol.2018.203158. Epub 2018 Oct 4.

  PMID: 30287621 BACKGROUND

• Della Porta MG, Garcia-Manero G, Santini V, Zeidan AM, Komrokji RS, Shortt J, Valcarcel D, Jonasova A, Dimicoli-Salazar S, Tiong IS, Lin CC, Li J, Zhang J, Pilot R, Kreitz S, Pozharskaya V, Keeperman KL, Rose S, Prebet T, Lai Y, Degulys A, Paolini S, Cluzeau T, Fenaux P, Platzbecker U. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024 Sep;11(9):e646-e658. doi: 10.1016/S2352-3026(24)00203-5. Epub 2024 Jul 19.

  PMID: 39038479 BACKGROUND

MeSH Terms

Conditions

Anemia, Refractory, with Excess of Blasts

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Anemia, Refractory; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Central Study Contacts

Sophie Park, Pr

CONTACT

0033476765697; Spark@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: September 21, 2026

Record last verified: 2026-09