Myelodysplastic Syndromes (MDS), Anemia
Conditions
Keywords
Myelodysplastic Syndromes, Anemia, SGLT2 inhibitor, Dapagliflozin, Lower-risk MDS
Brief summary
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
Dapagliflozin 10 mg administered orally once daily for 24 weeks.
Sponsors
Seug yun Yoon, MD
Boryung Pharmaceutical Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single-arm, open-label, phase II study in which all participants receive dapagliflozin 10 mg once daily for 24 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin Response Rate | Within 24 weeks | Proportion of patients achieving a hemoglobin increase of ≥1.0 g/dL from baseline, sustained for at least 8 weeks, in the absence of red blood cell transfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin Level | Up to 24 weeks | Mean change in hemoglobin level from baseline during the study period. |
| Proportion of Patients With Hemoglobin Increase ≥1.5 g/dL | Up to 24 weeks | Proportion of patients achieving a hemoglobin increase of ≥1.5 g/dL from baseline. |
| Change in Red Blood Cell Transfusion Requirement | Up to 24 weeks | Change in red blood cell transfusion requirement compared to baseline. |
| Duration of Hemoglobin Response | Up to 24 weeks | Duration from first documented hemoglobin response to loss of response. |
| Incidence of Adverse Events | Up to 24 weeks | Incidence and severity of adverse events assessed according to CTCAE criteria. |
Contacts
CONTACTSeug yun Yoon, MD, PhD
Outcome results
None listed