myeloproliferative neoplasm
Conditions
Interventions
Control group:Rucotinib + prednisone + danazol combined with thalidomide
Experimental group:Rucotinib + prednisone + danazol combined with ennatostat
Sponsors
Fujian Medical University Union Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be enrolled in this study: 1. age 18 to 90 years (including upper and lower limits), male or female; 2. a definitive diagnosis of primary myelofibrosis (PMF), post-positive erythrocytosis myelofibrosis (post-PV MF), or post-positive thrombocytosis myelofibrosis (post-ET MF) according to the 2022 WHO guidelines for the diagnosis of chromosome-negative MPN in Philadelphia, with screening/baseline bone marrow morphology and immunophenotyping of primitive cells = grade 2; 3. symptomatic anemia: HB = 2 times (>= 7 days apart), including transfusion-dependent subjects, i.e., transfusion load of >= 1 pRBC unit every 8 weeks; 4. not expected to undergo hematopoietic cell transplantation within 7 months of enrollment and have a life expectancy of at least 28 weeks; 5. an Eastern Cooperative Oncology Group (ECOG) physical status score of = 12 months and >= 50 years of age) are eligible to participate in the study; b. Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to the first dose on Day 1, and must agree to use adequate contraception (contraceptive success rate of at least 99%) from Screening through Safety Follow-Up. Available methods with a contraceptive success rate of at least 99% should be communicated to the subject and his/her understanding should be confirmed; c. Male subjects of childbearing potential must agree to use appropriate contraception (with a contraceptive success rate of at least 99%) from Screening until 93 days after the last dose of study drug and must not donate sperm during this time. Available methods of contraception with at least a 99% success rate should be communicated to the subject and his/her understanding should be verified; 7. be able to understand the procedures and methodology of this clinical trial and, with fully informed consent, the subject voluntarily participates and voluntarily signs an informed consent form in writing by himself/herself or legal representative; 8. the subject is willing and able to comply with the study visit schedule and other protocol requirements.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria are not eligible for enrollment: 1. other causes of anemia (e.g., iron deficiency anemia, B12 and folate deficiencies, hemolytic anemia, infections, or bleeding) 2. inadequate iron stores (ferritin 500 mIU/mL. 4. treatment with ESAs within 8 weeks prior to screening/enrollment. 5. has not fully recovered from the side effects/ or complications of major surgery prior to initiation of therapy. 6. recent history of inadequate bone marrow reserve (examples include, but are not limited to, the following): a. Platelet count 2.0 x upper limit of normal (ULN). Note: Subjects may be enrolled if total bilirubin > 2.0 x ULN and direct bilirubin 3 x ULN or CTCAE class >= 3 for hepatic impairment. 12. history of thromboembolic events such as stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism within 6 months prior to enrollment. 13. history of hypertension, or diastolic blood pressure >= 90 mmHg or systolic blood pressure >= 140 mmHg measured during Screening. and other uncontrolled severe or unstable cardiac disease that, in the opinion of the investigator, may jeopardize subject safety or compliance with the regimen. 14. known hypersensitivity or severe reaction to enalastat, placebo excipients. 15. active bacterial, fungal, parasitic or viral infection requiring treatment. Subjects with acute infections requiring treatment should have screening/enrollment delayed until the course of treatment is complete and the event is considered to have subsided. Prophylactic antibiotics or antivirals are permitted. 16. active chronic hepatitis B or C (HBV/HCV) infection requiring treatment, and known blood-borne infections such as HIV. 17. active alcohol or drug addiction that may interfere with compliance with study requirements. 18. the presence of conditions that, in the judgment of the Investigator, would interfere with full participation in the study (including administration of study drug and participation in required study visits, pose a significant risk to subjects, or interfere with the interpretation of study data. 19. has received any live vaccine within 30 days prior to the first dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Red lineage response rate;Proportion of subjects removed from transfusion dependence; | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to red lineage response ;Duration of red lineage response ;Second red lineage response rate;Changes in red blood cell transfusion unites;Frequency of alterations in red blood cell transfusion dependence;Duration of sustained response time to withdrawal from transfusion dependence;Changes in hemoglobin; | — |
Countries
China
Contacts
Public ContactYong Wu
Fujian Medical University Union Hospital
Outcome results
None listed