Clinical trial NCT06006949: Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory MDS-RS
Official title: Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory Myelodysplastic Syndrome With Ring Sideroblasts (MDS-RS): A Prospective Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Myelodysplastic Syndromes
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-08-23
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a randomized controlled phase II/III clinical trial, 58% of patients with lower-risk MDS had at least a 50% reduction in red blood cell (RBC) transfusion units every 8 weeks after roxadustat treatment. In a randomized controlled phase III clinical trial, luspatercept significantly improved transfusion dependence in erythropoietin-stimulating agents (ESA)-refractory MDS-RS and improved hemoglobin response and quality of life, compared to placebo. This study aimed to evaluate the efficacy and safety of roxadustat combined with luspatercept versus luspatercept monotherapy in the treatment of refractory MDS-RS.

Detailed description: Myelodysplastic neoplasms (MDS) are heterogeneous clonal disorders of stem cells that result in peripheral blood cytopenia and ineffective hematopoiesis, with the potential risk of the development of acute myeloid leukemia (AML). Most patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS) are stratified into lower-risk groups by the revised International Prognostic Scoring System (IPSS). At present, the main therapies for MDS-RS are red blood cell and platelet transfusion, erythropoietin (EPO), androgen, and iron chelation therapy. Roxadustat can up-regulate transferrin receptors to increase iron absorption, up-regulate transferrin to promote iron transport, and down-regulate ferritin levels to indirectly improve iron absorption and transport, promote plasma iron entry into the bone marrow to generate red blood cells and promote the production of EPO in the physiological range. Luspatercept generally promotes advanced erythrocyte maturation by inhibiting the TGF-β/smad2/3 signaling pathway. In a randomized controlled phase II/III clinical trial, 58% of patients with lower-risk MDS had at least a 50% reduction in red blood cell (RBC) transfusion units every 8 weeks after roxadustat treatment. In a randomized controlled phase III clinical trial, luspatercept significantly improved transfusion dependence in erythropoietin-stimulating agents (ESA)-refractory MDS-RS and improved hemoglobin response and quality of life, compared to placebo. The aim of this study was to evaluate the efficacy and safety of roxadustat combined with luspatercept versus luspatercept monotherapy in the treatment of refractory MDS-RS. If it is proved that the combination of the two drugs is better than luspatercept monotherapy, it can quickly improve the anemia of refractory MDS-RS and improve the quality of life.

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years old.
2. Patients with a definite diagnosis of MDS-RS and stratified as lower-risk according to IPSS-R.
3. After at least 6 weeks of rhEPO treatment, with hemoglobin\<100g/L
4. Adequate hepatic functions with alanine transaminase (ALT)/aspartate. transaminase (AST) levels within 2 times of the normal upper limit and total bilirubin levels within 2 times of the normal upper limit.
5. ECOG≤2 with an expected life span of more than 6 months
6. Documented patient consent.

Exclusion Criteria:

1. Age \<18 years old.
2. Complicated with active or uncontrolled infections.
3. Complicated with other malignancies.
4. Creatinine/transaminase ≥ 2 normal upper limit.
5. Complicated with myelofibrosis.
6. Pregnant or lactating women, or men with recent fertility needs
7. Allergic to luspatercept or excipients
8. Patients with history of polysorbate 80 allergy

Primary outcomes:
measure: overall response rate (ORR)
timeFrame: 6 month
Secondary outcomes:
measure: transfusion indenpendence (TI)
timeFrame: 6 month
measure: adverse event rate
timeFrame: 6 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
Study officials:
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