myelodysplastic syndromes
Conditions
Interventions
Experimental Group:Luspatercept by subcutaneously injection per 21 days, at a dose of 1 mg/kg titered to a maximum of 1.75 mg/kg
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subject is = 18 years of age the time of signing the informed consent form (ICF). 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 3. Documented diagnosis of MDS according to WHO 2022 classification[15], with SF3B1 mutation confirmed by sequencing. 4. Failure to HMAs as defined by any one of the following: • Failure to achieve complete or partial response or hematological improvement after at least six (azacitidine) or four (decitabine) 4-week treatment cycles administered during the past two years OR • Relapse after initial complete or partial response or hematological improvement observed after at least six (azacitidine) or four (decitabine) 4-week treatment cycles. OR • Progression (according to 2006 IWG criteria) at any time after initiation of AZA or DAC treatment 5. Requires RBC transfusions, as documented by the following criteria: • average transfusion requirement of = 2 units/8 weeks of RBCs confirmed for a minimum of 16 weeks immediately preceding enrollment. • no consecutive 56-day period that was RBC transfusion-free during the 16 weeks immediately preceding enrollment. 6. Ineligible, or opted not to participate in bone marrow transplantation. 7. No medical need for or patient opted not to receive induction chemotherapy. 8. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. 9. Females of childbearing potential (FCBP) must: • Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact. • Either commit to true abstinence* from heterosexual contact (which must be reviewed prior to each luspatercept administration or on a monthly basis [eg. in the event of dose delays] and source documented) or agree to use, and be able to comply with, effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy. Male subjects must: • Practice true abstinence (which must be reviewed prior to each luspatercept administration or on a monthly basis [eg. in the event of dose delays]) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy. 10. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion criteria
Exclusion criteria: 1. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011). 2. MDS associated with del 5q cytogenetic abnormality. 3. Secondary MDS, ie. MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases. 4. Prior allogeneic or autologous stem cell transplant. 5. Known history of diagnosis of AML 6. Estimated glomerular filtration rate (eGRF) or creatinine clearance < 40 mL/min 7. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) = 3.0 x upper limit of normal (ULN) 8. Total bilirubin = 2.0 x ULN. 9. Prior history of malignancies, other than MDS, unless the subject has been free of the disease for = 5 years. 10. History of stroke, deep venous thrombosis (DVT), pulmonary or arterial embolism within 6 months prior to enrollment. 11. Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator within 6 months prior to enrollment. 12. Uncontrolled systemic fungal, bacterial, or viral infection. 13. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product. 14. Major surgery within 8 weeks prior to enrollment. Subjects must have completely recovered from any previous surgery prior to enrollment. 15. Pregnant or breastfeeding females. 16. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 17. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 18. Subject has any condition or concomitant medication that confounds the ability to interpret data from the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Red Blood Cell Transfusion Independence (RBC-TI) =8 weeks; | — |
Secondary
| Measure | Time frame |
|---|---|
| RBC-TI = 12 weeks;RBC-TI = 16 weeks;Modified hematologic improvement - erythroid;Mean hemoglobin increase = 1.0 g/dL;Duration of RBC-TI;Health-related quality of life;Hematologic improvement neutrophils;Hematologic improvement platelets;Mean decrease in serum ferritin;Time to RBC-TI;Progression to AML;Progression free survival;Adverse events; | — |
Countries
China
Contacts
Public ContactGuangsheng He
The First Affiliated Hospital with Nanjing Medical University
Outcome results
None listed