Efficacy and Safety of Luspatercept: a Study by Fondazione Italiana Sindromi Mielodisplastiche

NCT05520749 | Completed

• 1 other identifier: FISiM-Luspatercept (ICH 3140)
• Study Type: observational
• Target: 215
• Locations: 1 country
• Sites: 1

Brief Summary

Myelodysplastic syndromes (MDS) are a group of malignancies characterized by reduced differentiation and increased apoptosis of hematopoietic progenitor cells, leading to ineffective hematopoiesis. Treatment of MDS varies according to prognosis. Patients with low IPSS-R risk have a low probability of progression to acute myeloid leukemia (AML) and the treatment is aimed at controlling cytopenia and improving quality of life (QOL). Anemia is the most common disease feature, occurring in 80%-85% of low-risk patients, 40% of whom eventually become RBC transfusion-dependent (TD). Luspatercept is a recombinant fusion protein that selectively binds to ligands belonging to the transforming growth factor-beta (TGF-beta) superfamily. Luspatercept binds to GDF11, GDF8, activin B, and other ligands. This binding leads to inhibition of Smad2/3 signaling, which is abnormally high in disease models of ineffective erythropoiesis such as MDS, resulting in erythroid maturation and differentiation. Luspatercept is now approved for the treatment of adult patients with TD anemia due to very low-, low-, and intermediate-risk MDS with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. FISiM (Fondazione Italiana Sindromi Mielodidplastiche) promotes a multicenter, retrospective observational study to collect information on the efficacy and safety of luspatercept in a real world Italian population of adult patients with transfusion-dependent anemia due to very low- and intermediate-risk MDS with ring sideroblasts

Conditions

Myeloid Dysplasia

Keywords

Luspatercept safety; Luspatercept efficacy; Real World Study

Outcome Measures

Primary Outcomes (1)

• Transfusion independence for 8 weeks or longer during weeks 1 through 24

  Percentage of patients who achieved RBC Transfusion Independence (RBC-TI) ≥ 8 weeks from week 1 to week 24. RBC-TI response is defined as the absence of any RBC transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Patients had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 date to qualify as a responder. Patients who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders. Data will be summarised as frequencies and proportions or as medians and range and differences will be estimated by the chi square test (the Fisher exact test when appropriated) or the t test (the Wilcoxon Mann Whitney U test and the ANOVA model when appropriated based on patient characteristics distribution).

  From week 1 through week 24 of treatment

Secondary Outcomes (3)

• Transfusion independence for 12 weeks or longer, assessed during weeks 1 through 24

  From Week 1 through Week 24 of treatment

• Transfusion independence for 12 weeks or longer, assessed during weeks 1 through 48

  From Week 1 through Week 48 of treatment

• Transfusion independence for 8 weeks or longer from week 1 through week 48

  From Week 1 through Week 48 of treatment

Other Outcomes (14)

• Erythroid response

  Week 1 through 24 or Week 1 Through Week 48

• Longest duration of primary response (week 1 through week 24)

  From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks

• Longest duration of primary response (week 1 through week 48)

  From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks

Study Arms (1)

Luspatercept treated patients

Adult patients (i.e. aged \>=18 years) with diagnosis of MDS according to WHO 2016 classification that met IPSS-R criteria for very low, low, or intermediate-risk MDS treated with Luspatercept

Drug: Luspatercept

Interventions

Luspatercept DRUG

Luspatercept treatment in adults with transfusion-dependent anaemia due to MDS

Luspatercept treated patients

Eligibility Criteria

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

Study Population

All patients treated with luspatercept in Italy between November 2020 and January 2022 will be included in this study (i.e., around 215 subjects).

You may qualify if:

• Adult patients (i.e. aged \>=18 years) with diagnosis of MDS according to WHO 2016 classification that met IPSS-R criteria for very low, low, or intermediate-risk MDS along with the following additional criteria:
• Ring Sideroblasts (RS) ≥15% of erythroid precursors in bone marrow in the absence of SF3B1 mutation, or ≥5% in the presence of SF3B1 mutation;
• Bone marrow blasts \<5%;
• Peripheral white blood cell count \<13,000/μL;
• ECOG PS 0-2;
• Refractory or intolerant to, or ineligible for prior ESA therapy.
• Required RBC transfusions per the following criteria:
• Mean RBC transfusion requirement ≥2 units/8 weeks in the 16 weeks before the start of luspatercept treatment
• No consecutive 56-day period free from RBCTs in the 16 weeks before the start of luspatercept treatment
• Treatment with luspatercept

You may not qualify if:

• Any prior treatment with the following therapies:
• Prior therapy with disease modifying agents for MDS including immunomodulatory drugs (eg, lenalidomide), hypomethylating agents (eg, azacitidine or decitabine), and immunosuppressive therapy.
• Presence of the following conditions:
• Pregnancy
• The following blood and laboratory parameters: ANC \<500/μL and Platelets \<50,000/μL

Sponsors & Collaborators

• Fondazione Italiana Sindromi Mielodisplastiche-ETS: lead
• Istituto Clinico Humanitas: collaborator

Study Sites (1)

Istituto Clinico Humanitas

Milan, Rozzano, 20089, Italy

Location

Related Publications (1)

• Lanino L, Restuccia F, Perego A, Ubezio M, Fattizzo B, Riva M, Consagra A, Musto P, Cilloni D, Oliva EN, Palmieri R, Poloni A, Califano C, Capodanno I, Itri F, Elena C, Fozza C, Pane F, Pelizzari AM, Breccia M, Di Bassiano F, Crisa E, Ferrero D, Giai V, Barraco D, Vaccarino A, Griguolo D, Minetto P, Quintini M, Paolini S, Sanpaolo G, Sessa M, Bocchia M, Di Renzo N, Diral E, Leuzzi L, Genua A, Guarini A, Molteni A, Nicolino B, Occhini U, Rivoli G, Bono R, Calvisi A, Castelli A, Di Bona E, Di Veroli A, Ferrara F, Fianchi L, Galimberti S, Grimaldi D, Marchetti M, Norata M, Frigeni M, Sancetta R, Selleri C, Tanasi I, Tosi P, Turrini M, Giordano L, Finelli C, Pasini P, Naldi I, Santini V, Della Porta MG; Fondazione Italiana Sindromi Mielodisplastiche (FISiM) Clinical network (https://www.fisimematologia.it/). Real-world efficacy and safety of luspatercept and predictive factors of response in patients with lower risk myelodysplastic syndromes with ring sideroblasts. Am J Hematol. 2023 Aug;98(8):E204-E208. doi: 10.1002/ajh.26960. Epub 2023 May 24. No abstract available.

  PMID: 37222267 DERIVED

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

Study Officials

• Matteo Della Porta, MD

  Istituto Clinico Humanitas

  STUDY DIRECTOR

• Valeria Santini, MD

  Università degli studi di Firenze - AOU Careggi

  STUDY CHAIR

• Lorenza Borin, MD

  ASST-MONZA

  PRINCIPAL INVESTIGATOR

• Daniela Cilloni, MD

  Aziena Ospedaliera Mauriziano - Torino

  PRINCIPAL INVESTIGATOR

• Bruno Fattizzo, MD

  Ospedale Policlinico di Milano

  PRINCIPAL INVESTIGATOR

• Pellegrino Musto, MD

  Policlinico di Bari

  PRINCIPAL INVESTIGATOR

• Esther Oliva, MD

  Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli di Reggio Calabria

  PRINCIPAL INVESTIGATOR

• Marta Riva, MD

  ASST Grande Ospedale Metropolitano Niguarda

  PRINCIPAL INVESTIGATOR

• Prassede Salutari, MD

  Presidio Ospedaliero Pescara

  PRINCIPAL INVESTIGATOR

• Maria Teresa Voso, MD

  Università Cattolica del Sacro Cuore - Roma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: August 30, 2022
• Study Start: January 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: January 31, 2023
• Last Updated: March 4, 2025

Record last verified: 2023-02

Locations

IT (1)