OncoMatch/Clinical Trials/NCT05924100
Efficacy and Safety of Luspatercept for the Treatment of Anemia Due to MDS With del5q, Refractory/Resistant/Intolerant to Prior Treatments, RBC-TD
Is NCT05924100 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies Luspatercept for myelodysplastic syndromes.
Treatment: Luspatercept — Myelodysplastic syndromes, primarily affecting older adults, are a heterogeneous group of clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis that manifest clinically as anemia, neutropenia, and/or thrombocytopenia of variable severity; these often result in RBC- transfusion dependent (TD) anemia, increased risk of infection, and/or hemorrhage, as well as a potential to progress to acute myeloid leukemia (AML). Lenalidomide is approved for red blood cell transfusion-dependent (RBC TD) anemia due to low-risk myelodysplastic syndromes (MDS) with a chromosome 5q deletion (del5q) with or without additional cytogenetic abnormalities. About one third of patients are refractory/resistant/intolerant and will require further treatment options. Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor type IIB (ActRIIB) linked to the Fc portion of human immunoglobulin G1 (IgG1-Fc). Luspatercept acts on endogenous inhibitors of late-stage erythropoiesis (eg, growth differentiation factor 11, GDF11) to increase release of mature erythrocytes into circulation. Nonclinical data have demonstrated that luspatercept binds to negative regulators governing late-stage erythroid development to inhibit their action, thereby promoting the maturation of erythrocytes in the bone marrow. Luspatercept is indicated for the treatment of adult patients with transfusion-dependent anaemia associated with beta-thalassaemia and 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. It is not indicated for other MDS subtypes. Unfortunately, patients with MDS with del5q refractory/resistant/intolerant to lenalidomide are excluded from clinical trials that evaluate novel treatments for the anemia of RBC TD lower risk MDS. Therefore, treatment of anemia in such patients is an unmet need. QOL-ONE Phoenix is a Phase 2, multicenter, single arm, prospective study. The primary objective of the study is to evaluate the effect of luspatercept on RBC TI in subjects with MDS with del5q with IPSS-R very low, low, or intermediate risk and \< 5% bone marrow blasts, resistant/refractory/intolerant to lenalidomide and who require RBC transfusions. The study is divided into a Screening Period, a 2-year Treatment Period and a 3-year Follow-up Period. Primary objective is to evaluate the effect of luspatercept on RBC TI (lack of transfusions for 8 consecutive weeks within the first 24 weeks) in subjects with MDS with del5q with IPSS-R very low, low, or intermediate risk and \< 5% bone marrow blasts, resistant/refractory/intolerant to lenalidomide and RBC TD.
Check if I qualifyExtracted eligibility criteria
Cancer type
Myelodysplastic Syndrome
Biomarker criteria
Excluded: TP53 mutation
Disease stage
Required: Stage VERY LOW, LOW, INTERMEDIATE (IPSS-R)
IPSS-R classification (Greenberg, 2012) of very low, low, or intermediate risk disease
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: erythropoiesis-stimulating agent
Refractory or intolerant to, or ineligible for, prior ESA treatment
Must have received: lenalidomide (lenalidomide)
Refractory or intolerant to, or ineligible for, prior lenalidomide treatment
Cannot have received: hypomethylating agent
Exception: subjects who previously received HMA may be enrolled at the investigator's discretion contingent that the subject received no more than 1 dose of HMA; last dose must be ≥ 5 weeks from the date of screening
Prior therapy with disease modifying agents for underlying MDS disease (hypomethylating agents)
Cannot have received: luspatercept (luspatercept)
Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
Cannot have received: sotatercept (sotatercept)
Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
Cannot have received: allogeneic stem cell transplant
Prior allogeneic or autologous stem cell transplant
Cannot have received: autologous stem cell transplant
Prior allogeneic or autologous stem cell transplant
Cannot have received: cytotoxic chemotherapy
Use of any of the following within 5 weeks prior to study entry: anticancer cytotoxic chemotherapeutic agent or treatment
Cannot have received: corticosteroid
Exception: except for subjects on a stable or decreasing dose for ≥ 1 week prior to study entry for medical conditions other than MDS
Use of any of the following within 5 weeks prior to study entry: corticosteroid
Cannot have received: iron-chelating agent
Exception: except for subjects on a stable or decreasing dose for at least 8 weeks prior to screening
Use of any of the following within 5 weeks prior to study entry: iron-chelating agents
Cannot have received: RBC hematopoietic growth factor
Use of any of the following within 5 weeks prior to study entry: other RBC hematopoietic growth factors
Cannot have received: investigational drug or device
Exception: if the half-life of the previous investigational product is known, use within 5 times the half-life prior to screening or within 5 weeks, whichever is longer is excluded
Use of any of the following within 5 weeks prior to study entry: investigational drug or device, or approved therapy for investigational use
Lab requirements
Blood counts
< 5% blasts in bone marrow; Peripheral blood WBC count <13,000/μL; Platelet counts below 50000/mmc or absolute neutrophil count below 500/mmc at the start of lenalidomide treatment = lenalidomide ineligible
Kidney function
Estimated glomerular filtration rate (eGFR) or creatinine clearance < 40 mL/min [excluded]
Liver function
Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase or alanine aminotransferase/serum glutamic pyruvic transaminase ≥ 3.0 x upper limit of normal (ULN) [excluded]; Total bilirubin ≥ 2.0 x ULN [excluded], higher levels acceptable if due to ineffective erythropoiesis or Gilbert Syndrome
Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase or alanine aminotransferase/serum glutamic pyruvic transaminase ≥ 3.0 x upper limit of normal (ULN) [excluded]; Total bilirubin ≥ 2.0 x ULN [excluded], higher levels acceptable if due to ineffective erythropoiesis or Gilbert Syndrome; Estimated glomerular filtration rate (eGFR) or creatinine clearance < 40 mL/min [excluded]; < 5% blasts in bone marrow; Peripheral blood WBC count <13,000/μL
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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