myeloproliferative neoplasms
Conditions
Interventions
A:Azacitidine + Ruxolitinib + Venetoclax (ARV regimen)
B:Azacitidine + Ruxolitinib (AR regimen)
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18-60 years at the time of screening; 2. Previous diagnosis of Ph- myeloproliferative neoplasm according to the 2016 World Health Organization criteria (including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF) and post-essential thrombocythemia myelofibrosis (Post-ET MF ) )patients; 3. Bone marrow examination within 4 weeks prior to enrollment with peripheral blood/bone marrow blasts (myeloblasts + monoblasts + promonocytes) >= 10%; 4. Spleen under the left costal margin is palpable on physical examination at screening and active MF-related symptoms are present at screening with a total symptom score(TSS) >= 10 as assessed using the MF Symptom Assessment Form; 5. Subjects have an Eastern Cooperative Oncology Group (ECOG) physical status score of 0, 1 or 2 at screening; 6. Screening bone marrow biopsy specimen and pathology report obtained within the past 4 weeks or willingness to undergo bone marrow aspiration and biopsy at screening/baseline; willingness to undergo bone marrow aspiration and biopsy every treatment course; 7. Life expectancy for at least 24 weeks; 8. Subjects are willing to avoid pregnancy or childbirth.
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to Ruxolitinib or to Venetoclax, Azacitidine or any other excipient; 2. Subjects with prior or planned hematopoietic stem cell transplantation; 3. Subjects who have previously received treatment with Venetoclax or Azacitidine, and cytotoxic drug chemotherapy (except hydroxyurea); 4. Inability to swallow food or any condition in the upper gastrointestinal tract that prevents the administration of oral drugs; 5. Hepatic insufficiency at the screening visit, as evidenced by: (1) Direct bilirubin >= 2.0 x Upper Limit of Normal (ULN) (Note: Direct bilirubin was measured only if total bilirubin was >= 2.0 x ULN.); (2) Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 2.5 x ULN; 6. Renal insufficiency at the screening with creatinine clearance <= 50 mL/min as estimated by the Cockcroft-Gault formula. Creatinine clearance thresholds based on the Cockcroft-Gault formula for mild, moderate and severe renal insufficiency are 60 to 90 mL/min, 30 to 59 mL/min and 0 to 29 mL/min, respectively. If the investigator prefers, he/she may use the measured creatinine clearance instead of the estimated value; 7. Subjects with a clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy. Subjects with acute infections requiring treatment should delay screening/enrollment until the treatment is completed and the event is considered to have subsided. Prophylactic antibiotics are allowed. Active HBV, HCV infection, or at risk of HBV reactivation requiring treatment. HBV DNA and HCV RNA must be undetectable. The risk of HBV reactivation is defined as a positive Hepatitis B surface antigen (HBsAg) or positive anti-hepatitis B core antibody (HBcAb); 8. HIV antibody positivity; 9. Uncontrolled severe or unstable cardiac disease that the investigator believes may jeopardize the safety of the subject or compliance with the protocol; 10. Active aggressive malignancy within the past 2 years except for treated basal or squamous cell carcinoma of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary and follicular carcinoma of the thyroid. Subjects with cured inert tumors (e.g., prostate cancer treated with radiation therapy or surgery) may be enrolled; 11. Active alcohol or drug addiction that may interfere with compliance with study requirements; 12. Has not recovered sufficiently from the toxicity and/or complications of major surgery prior to initiation of treatment; 13. Currently breastfeeding or pregnant; 14. There are circumstances that, in the judgment of the investigator, would interfere with full study participation (including study drug administration and participation in required study visits); pose a significant risk to the subject; or interfere with the interpretation of study data; 15. Subjects are unable to understand or unwilling to sign an Informed Consent Form (ICF); 16. Received any live vaccine within 30 days prior to the first dose of the study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete response, CR;CR with incomplete count recovery, CRi; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;relapse-free survival;safety and tolerability; | — |
Countries
China
Contacts
Public ContactXiao Zhijian
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical
Outcome results
None listed