Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory MDS-RS

August 17, 2023 updated by: Bing Han, Peking Union Medical College Hospital

Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory Myelodysplastic Syndrome With Ring Sideroblasts (MDS-RS): A Prospective Randomized Controlled Study

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Peking Union Medical College Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: roxadustat and luspatercept

Luspatercept (1.0 mg/kg, subcutaneously injection every 3 weeks, adjusted according to blood pattern, up to 1.75mg/kg.

Roxadustat (150mgqod) was administered for at least 6 months to evaluate efficacy.

Hemoglobin ≥120g/L can be discontinued, and hemoglobin <120g/L can continue to use. Those who are effective will continue to be given the combination therapy until ineffective or intolerant.
Drug: Roxadustat
Roxadustat (150 mgqod)
Drug: Luspatercept
Luspatercept (1.0 mg/kg, subcutaneously injection every 3 weeks, adjusted according to blood pattern, up to 1.75mg/kg)
Experimental: luspatercept

Luspatercept (1.0 mg/kg, subcutaneously injection every 3 weeks, adjusted according to blood pattern, up to 1.75mg/kg.

Luspatercept was given for at least 6 months to evaluate the efficacy. Hemoglobin ≥120g/L can be discontinued, and hemoglobin <120g/L can continue to use. Those who are effective will continue to be given the therapy until it is ineffective or intolerant
Drug: Luspatercept
Luspatercept (1.0 mg/kg, subcutaneously injection every 3 weeks, adjusted according to blood pattern, up to 1.75mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall response rate (ORR)
Time Frame: 6 month
Proportion of patients who achieved complete response, partial response and hematological response.
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
transfusion indenpendence (TI)
Time Frame: 6 month
Proportion of patients with transfusion dependence over 8 weeks
6 month
adverse event rate
Time Frame: 6 month
Proportion of patients with adverse events
6 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2023

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2025

Study Registration Dates

First Submitted

August 17, 2023

First Submitted That Met QC Criteria

August 17, 2023

First Posted (Actual)

August 23, 2023

Study Record Updates

Last Update Posted (Actual)

August 23, 2023

Last Update Submitted That Met QC Criteria

August 17, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Lus-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndromes

Clinical Trials on Roxadustat

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Kingdom

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe