AZA+Lus VS AZA Monotherapy in HR-MDS

Azacitidine Plus Luspatercept Versus Azacitidine Monotherapy in Higher-risk Myelodysplastic Neoplasms: a Randomized Prospective Study

This study is a randomized, prospective, single-center, open-label cohort study involving untreated HR-MDS patients. The patients were divided randomized into AZA+Lus cohort and AZA monotherapy cohort.

Study Overview

• Status: Not yet recruiting
• Conditions: Higher-risk Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Azacitidine (AZA); Drug: Luspatercept

Detailed Description

The hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DEC) have been shown to improve survival and delay disease progression in patients with high-risk MDS. They are recommended by the NCCN as first-line treatments for patients with high-risk MDS. Clinical trials have demonstrated an OR rate of approximately 40-50% with AZA in patients with high-risk MDS. Despite the efficacy of HMA therapy, the rate of transfusion independence remains low. Anemia remains the most prominent symptom in refractory patients, with very limited options for subsequent treatment. Prolonged anemia affects every organ function and seriously affects the prognosis of patients.

Luspatercept is currently approved for the treatment of patients with both erythropoiesis receptor agonist ( ESA) treatment failures in transfusion-dependent low-risk MDS-RS patients. In a randomized controlled phase III clinical trial, compared to a placebo group, luspatercept significantly improved transfusion dependence and improved hemoglobin and quality of life in refractory MDS-RS patients. A recent conference report suggested that there was no significant difference in efficacy between low-risk and high-risk patients treated with luspatercept and that the HI rate for high-risk patients treated with luspatercept monotherapy was approximately 50%.

Thus this study aimed to compare the efficacy of AZA+luspatercept and AZA monotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years old
• Diagnosed as higher-risk MDS (IPSS intermediate-2/high-risk, or IPSS-R >3.5, or IPSS-M moderate high-, high-, very high-risk)
• Untreated patients
• Liver and kidney function less than 2 times of upper limit of normal
• ECOG≤2 and expected survival more than 6 months
• Informed consent signed

Exclusion Criteria:

• With active infection
• Other malignant tumors
• Obvious abnormal liver and kidney function, or abnormal function of other organs
• Combined with myelofibrosis
• Have undergone bone marrow transplantation
• Pregnant or lactating women, or men who have recent reproductive needs
• Allergic to azacytidine, Rotercept or excipients
• History of polysorbate 80 allergy
• Refuse to sign informed consent
• Researchers consider it inappropriate to participate in the experiment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azacitidine+Luspatercept	Drug: Azacitidine (AZA); Azacitidine 75mg/m/ day *5 days, 28 days for 1 course; Drug: Luspatercept; Luspatercept 1.0 mg/kg subcutaneously every 3 weeks, adjusted according to hemoglobin, up to 1.75mg/kg. If hemoglobin ≥120g/L, luspatercept can be discontinued.
Active Comparator: Azacitidine	Drug: Azacitidine (AZA); Azacitidine 75mg/m/ day *5 days, 28 days for 1 course

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall response rate	3 months, 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	through study completion, an average of 1 year
complete response rate	3 months, 6 months
rate of transfusion independence	3 months, 6 months
adverse event rate	through study completion, an average of 1 year
relapse rate	through study completion, an average of 1 year
progress-free survival	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 13, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 13, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: azacitidine; luspatercept; higher-risk myelodysplastic syndrome
• Additional Relevant MeSH Terms: Neoplasms; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Preleukemia; Myelodysplastic Syndromes; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Hematinics; Luspatercept; Azacitidine
• Other Study ID Numbers: AZA-Lus-HRMDS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No