bone marrow fibrosis-associated anemia
Conditions
Interventions
Experimental Group:Upon enrollment, subjects will receive the selinexor combined with luspatercept regimen: the standard dose of selinexor is 20mg twice weekly, and will be reduced to 20mg once weekly
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Inclusion criteria
Inclusion criteria: 1. Subject aged >= 18 years at 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 bone marrow fibrosis, including MF, MDS-f, MDS/MPN with secondary myelofibrosis, according to WHO 2022 classification; 4. MDS-f or MDS/MPN with secondary myelofibrosis, not suitable for ruxolitinib; OR myelofibrosis failed to ruxolitinib, which is defined as following: with normal therapeutic dose of ruxolitinib for over 3 months, the patient's constitutional symptoms and spleen volume were not reduced significantly, and the quality of life was negatively affected. Or with supportive care for anemia, the patient still has drug-related anemia or needs red blood cell transfusions; Or the dose of ruxolitinib should be adjusted to below the normal therapeutic dose (= 2 units/8 weeks of RBCs confirmed for a minimum of 16 weeks immediately preceding enrollment; (2) 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. Use of hydroxyurea or other drugs with potential effects on hematopoiesis, or persistent adverse events from =8 weeks of prior treatment to the enrollment date. 2. Anemia caused by iron deficiency, B12 and folate deficiency, hemolytic anemia, infection or bleeding. 3. Pregnant or breastfeeding women. 4. Subjects underwent major surgery within 8 weeks before enrollment. Subjects must have fully recovered from any surgery immediately prior to enrollment. 5. Subject has a prior history of malignant tumors, unless subject has been free of the disease for =5 years. However, items that meet the following historical/concurrent criteria are permitted: incidental histological findings of basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, cancer in situ of the prostate (using stage T1a or T1b of the tumor, lymph node, metastatic [TNM] clinical staging system) 6. Subjects with a history of hematopoietic cell transplantation. 7. The subject has the following laboratory abnormalities: Estimated glomerular filtration rate 3.0 times the upper limit of normal (ULN) Direct bilirubin =2 times the upper limit of normal 8. Subjects had stroke, deep vein thrombosis, pulmonary or arterial embolism within 6 months prior to enrollment. 9. Myocardial infarction, uncontrolled angina pectoris, uncontrolled heart failure, or uncontrolled arrhythmia identified by the investigator within 6 months prior to inclusion. 10. Subjects with severe allergy or history of allergic reaction or hypersensitivity to recombinant proteins or excipients in the test product. 11. Uncontrolled systemic fungal, bacterial, or viral infection (defined as persistent signs/symptoms associated with infection despite no improvement with appropriate antibiotics, antiviral therapy, and/or other treatment). 12. The subject has evidence of human immunodeficiency virus (HIV), active hepatitis B (HepB) and/or active hepatitis C (HepC). 13. Subject has any significant physical condition, laboratory abnormality, mental illness, or local regulations that are considered vulnerable (such as incarceration or institution) that will prevent subject from participating in the study. 14. The subject has any condition, including laboratory abnormalities, that he/she would be at unacceptable risk if he/she participated in the study. 15. The subject has any medical condition or concomitant medication that affects the ability to interpret the study data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Red Blood Cell Transfusion Independence (RBC-TI) >= 8 weeks; | — |
Secondary
| Measure | Time frame |
|---|---|
| Red Blood Cell Transfusion Independence (RBC-TI) >= 12 weeks;Overall response;Modified hematologic improvement - erythroid;Mean hemoglobin increase >= 1.0 g/dL;Duration of RBC-TI;Health-related quality of life;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