Dapagliflozin for Anemia in Lower-Risk Myelodysplastic Syndromes

Official title

A Phase II, Prospective, Open-Label Study to Evaluate the Efficacy and Safety of Dapagliflozin for Anemia in Patients With Lower-Risk Myelodysplastic Syndromes

Overview

This study is a prospective, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of dapagliflozin in improving anemia in patients with lower-risk myelodysplastic syndromes (MDS). Anemia is the most common clinical problem in patients with lower-risk MDS and often leads to fatigue, reduced quality of life, and the need for repeated blood transfusions. Current treatment options, including erythropoiesis-stimulating agents and other therapies, are not effective in all patients, and additional treatment options are needed. Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that is widely used for the treatment of diabetes, heart failure, and chronic kidney disease. Previous studies have shown that SGLT2 inhibitors can increase hemoglobin levels, possibly by stimulating erythropoiesis. In this study, eligible patients will receive dapagliflozin 10 mg orally once daily for 24 weeks. The primary objective is to evaluate the hemoglobin response rate during the study period. Secondary objectives include changes in hemoglobin levels, transfusion requirements, and safety outcomes. This study aims to explore whether dapagliflozin can serve as a potential treatment option for anemia in patients with lower-risk MDS.

Detailed description

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis and cytopenias. Among these, anemia is the most common and clinically significant manifestation in patients with lower-risk MDS, often leading to fatigue, decreased quality of life, and increased transfusion requirements.

Current treatment options for anemia in lower-risk MDS include erythropoiesis-stimulating agents (ESA) and other therapies such as luspatercept. However, these treatments are not universally effective, and access may be limited in certain settings. As a result, many patients remain transfusion-dependent or experience persistent anemia, highlighting the need for additional therapeutic options.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in the management of diabetes mellitus, heart failure, and chronic kidney disease. Multiple clinical studies have consistently demonstrated increases in hemoglobin and hematocrit levels in patients receiving SGLT2 inhibitors. The proposed mechanisms include increased erythropoietin production, modulation of iron metabolism, and reduction in plasma volume. These findings suggest a potential role of SGLT2 inhibitors in stimulating erythropoiesis.

Recent observational data have suggested that SGLT2 inhibitor therapy may improve hemoglobin levels in patients with myeloid neoplasms, including MDS. However, these findings are limited by small sample sizes and retrospective study designs, and prospective clinical data are lacking.

This study is designed as a prospective, single-arm, phase II clinical trial to evaluate the efficacy and safety of dapagliflozin in patients with lower-risk MDS and anemia. Participants will receive dapagliflozin 10 mg orally once daily for 24 weeks. The study will assess hemoglobin response, transfusion requirements, and safety outcomes over the study period.

The results of this study are expected to provide proof-of-concept evidence for the use of SGLT2 inhibitors as a potential therapeutic option for anemia in patients with lower-risk MDS and to support further clinical development in this setting.

Interventions

• Drug Dapagliflozin (10mg Tab)
  Dapagliflozin 10 mg administered orally once daily for 24 weeks.

Primary outcome measures

• Hemoglobin Response Rate [Time frame: Within 24 weeks]

Secondary outcome measures (5)

• Change in Hemoglobin Level [Time frame: Up to 24 weeks]
• Proportion of Patients With Hemoglobin Increase ≥1.5 g/dL [Time frame: Up to 24 weeks]
• Change in Red Blood Cell Transfusion Requirement [Time frame: Up to 24 weeks]
• Duration of Hemoglobin Response [Time frame: Up to 24 weeks]
• Incidence of Adverse Events [Time frame: Up to 24 weeks]

Eligibility criteria

Inclusion criteria

• Adults aged ≥18 years
• Diagnosis of myelodysplastic syndromes (MDS) according to WHO or ICC criteria
• Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate risk
• Hemoglobin ≤10 g/dL at screening
• Transfusion independent or low transfusion burden (Defined as ≤2 units of red blood cell transfusion within 8 weeks prior to enrollment)
• If receiving erythropoiesis-stimulating agents (ESA) or other anemia-directed therapy, on a stable dose for at least 8 weeks prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) ≥0.75 ×10⁹/L
• Platelet count ≥50 ×10⁹/L
• Adequate organ function:

Creatinine clearance ≥30 mL/min AST or ALT ≤3 × upper limit of normal

Exclusion criteria

• IPSS-R intermediate-high or high-risk MDS
• Transformation to acute myeloid leukemia or ≥20% blasts
• Initiation or dose change of MDS- or anemia-directed therapy (e.g., ESA, luspatercept, hypomethylating agents) within 8 weeks prior to screening
• Red blood cell transfusion >2 units within 8 weeks prior to enrollment
• Current use of SGLT2 inhibitors or history of serious adverse reaction to SGLT2 inhibitors
• Uncontrolled diabetes mellitus (e.g., HbA1c >10%) or history of diabetic ketoacidosis
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²
• Active or uncontrolled infection
• Absolute neutrophil count (ANC) <0.75 ×10⁹/L or platelet count <50 ×10⁹/L
• Pregnant or breastfeeding women
• Any condition that, in the investigator's judgment, would make participation inappropriate

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mazer CD, Hare GMT, Connelly PW, Gilbert RE, Shehata N, Quan A, Teoh H, Leiter LA, Zinman B, Juni P, Zuo F, Mistry N, Thorpe KE, Goldenberg RM, Yan AT, Connelly KA, Verma S. Effect of Empagliflozin on Erythropoietin Levels, Iron Stores, and Red Blood Cell Morphology in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation. 2020 Feb 25;141(8):704-707. doi: 10.1161/CIRCULAT PMID 31707794
• Alsugair A, Fathima S, Aperna F, Gangat N, Tefferi A. Sodium-glucose co-transporter-2 inhibitor treatmentassociated changes in hemoglobin level in anemic patients with myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms. Haematologica. 2025 Jun 1;110(6):1422-1425. doi: 10.3324/haematol.2024.287032. Epub 2025 Jan 23. No abstract available. PMID 39844769

Identifiers

NCT: NCT07516847 · DAPA-MDS-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗