The Tapering Dose of Luspatercept in Patients With Lower-risk Myelodysplastic Syndromes

Safety and Efficacy Study of the Tapering Dose of Luspatercept in Patients With Lower-risk Myelodysplastic Syndromes

This is a prospective, single center, single-arm, phase 2 study. The aim of this study is to evaluate the efficacy and safety of Luspatercept for Patients with Lower-risk Myelodysplastic Syndromes (MDS).

Study Overview

• Status: Recruiting
• Conditions: Lower Risk MDS Per IPSS-R
• Intervention / Treatment: Drug: Luspatercept

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhen Gao; Phone Number: ‭15522360862‬; Email: gaozhen@ihcams.ac.cn
• Study Contact Backup: Name: Jingyu Zhao; Phone Number: 13752253515; Email: zhaojingyu@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300131
      • Recruiting
      • Regenerative Medicine Center
      • Contact: Zhen Gao, MD; Phone Number: 13752253515; Email: gaozhen@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female age ≥ 18 years
• Subject has diagnosis of MDS according to WHO classification that meets IPSS-R score ≤3.5
• Hemoglobin < 100g/L at baseline
• Refractory or intolerant to prior ESA treatment or EPO≥500U/L
• ECOG performance status ≤2
• Willing and able to comply with the requirements for this study and written informed consent.

Exclusion Criteria:

• Platelet counts < 50 x 10^9/L
• Previously treated with either luspatercept or sotatercept

• Use any of the following prior to this study

  • Immunomodulatory drugs such as lenalidomide [IMiD] for ≥4 weeks
  • Immunosuppressive therapy [IST] for ≥4 weeks
  • Demethylating agents [HMA] ≥ 1 cycle of treatment
• MDS associated with del 5q cytogenetic abnormality
• Secondary MDS, i.e. MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding.
• Prior allogeneic or autologous stem cell transplant.
• Prior history of malignancies, other than MDS, unless the subject is free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed: basal or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasia, carcinoma in situ of the cervix or other indolent tumors.
• Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment), known human immunodeficiency virus (HIV), known evidence of active infectious hepatitis B, and/or known evidence of active hepatitis C.
• Clinically significant cardiac disease, including any of the follow: uncontrolled angina pectoris, myocardial infarction, unstable cardiac arrhythmias, congestive heart failure and New York Heart Association (NYHA) grade 2-4 cardiac failure.
• Abnormal liver function: two consecutive examinations with an interval of ≥1 week suggest that ALT and AST are 2.5 times higher than the upper limit of normal values
• Renal impairment: creatinine clearance <60ml/min
• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study, including clinically significant cardiac diseases, refractory hypertension, metabolic disorders and other diseases that seriously affect the function of the gastrointestinal tract.
• Had a history of any psychiatric diseases, cerebrovascular disease or cognitive sequelae of head injury.
• Major surgery within 8 weeks prior to this study. Subjects must be completely recovered from any previous surgery prior to this study.
• Received attenuated vaccine in 4 weeks before enrollment.
• Participation in another clinical trial within 4 weeks before the start of this trial.
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the luspatercept.
• Pregnant or breast-feeding patients
• Patients considered to be ineligible for the study by the investigator for reasons other than the above.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Luspatercept; open-label, single-arm	Drug: Luspatercept; The starting dose is 1.75mg/kg once every 3 weeks by subcutaneous injection. For rapid hemoglobin rise after 2 consecutive doses at the 1.75mg/kg starting dose, decrease the dose of Luspatercept or interrupt treatment. Otherwise, continue treatment with the dose of 1.75mg/kg once every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects achieving hematologic improvement - erythroids (HI-E) according to IWG 2006 criteria	within 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving RBC-TI according to IWG 2006 criteria		within 12 weeks
Median time to HI-E or RBC-TI		within 12 weeks
Mean change in serum ferritin		within 12 weeks
Incidence of the adverse event	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event.	within 12 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: Beijing Health Alliance Charitable Foundation

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: June 21, 2023
• First Submitted That Met QC Criteria: June 21, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia; Hematinics; Luspatercept
• Other Study ID Numbers: Lusp-MDS

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