myelofibrosis
Conditions
Interventions
Single arm:1
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1.Male or female patients aged 18-65 years at the time of screening who provide written informed consent.2.Patients with a diagnosis of DIPSS intermediate-1, intermediate-2, high-risk PMF, PPV-MF, or PET-MF according to the 2016 World Health Organization criteria.3.Treated with ruxolitinib for >=3 months, receiving a stable dose for at least 8 weeks prior to day 1 (may receive a dose of 5 mg twice daily to 25 mg twice daily, split dosing [total daily dose of at least 10 mg] is allowed, once daily is not allowed). 4.Evidence of poor efficacy of ruxolitinib [both (1) and (2) must be met]: (1) The spleen is palpable = 5 cm below the left costal margin on physical examination at the screening visit, and (2) MF-related active symptoms are present at the screening visit, and the total symptom score (TSS)>=10 as assessed using Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). 5.Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 ,or 2 at Screening. 6.Screening bone marrow biopsy specimen and pathology report obtained within the past 2 months or willingness to undergo bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at week 24 and every 24 weeks thereafter. Screening/baseline bone marrow biopsy specimens must show the diagnosis of MF.7.Life expectancy for at least 24 weeks.8.Subjects are willing to avoid pregnancy or childbirth based on the following criteria. (1) Infertile female subjects (i.e. surgically sterilized by hysterectomy and/or bilateral oophorectomy or amenorrhea for >= 12 months and >= 50 years of age) are eligible to participate in the study. (2) Fertile female subjects must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result prior to the first dose of study drug on Day 1 and must agree to use effective contraception measures from screening to safety follow-up. (3) Fertile male subjects must agree to use effective contraception measures from screening to 6 months after the last dose of study drug and during this period no sperm donation is allowed.
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to ruxolitinib or to ACT001 or any other excipient. 2. Subjects who have previously received treatment with a JAK inhibitor other than ruxolitinib. 3. Subjects with prior or planned hematopoietic stem cell transplantation (HSCT). 4. Treatment with an experimental drug against MF or any other standard drug used for MF (e.g., danazol, hydroxyurea) (except ruxolitinib) within 3 months prior to initiation of study drug therapy and/or all toxicity from prior therapy (except ruxolitinib) has not returned to Grade 1 or better; 5. Inability to swallow food or any condition in the upper gastrointestinal tract that prevents the administration of oral drugs. 6. Recent history of inadequate bone marrow reserve as evidenced by: (1) Platelet count 10% at screening or baseline hematology. (4) Reluctance to receive RBC transfusions for low hemoglobin levels. 7. Subjects with inadequate liver function, as evidenced by: (1) Direct bilirubin >=2.0 * Upper Limit of Normal (ULN) (Note: direct bilirubin is measured only if total bilirubin is >=2.0*ULN). (2) Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >2.5*ULN. 8. Subjects with inadequate renal function, with estimated creatinine clearance rate =50mL/min. Based on the Cockcroft-Gault formula, the threshold creatinine clearance rate 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 rate instead of the estimated value. 9. 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). 10. HIV antibody positivity. 11. Uncontrolled severe or unstable cardiac disease that the investigator believes may jeopardize the safety of the subject or compliance with the protocol. 12. 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. 13. Received splenic radiotherapy within 6 months prior to the first dose of the study drug. 14. Active alcohol or drug addiction that may interfere with compliance with study requirements. 15. Use of any potent CYP3A4 inhibitor or inducer within 14 days or 5 half-lives (whichever is longer) prior to the first dose of the study drug or expected during the study period. 16. Has not recovered sufficiently from the toxicity and/or complications of major surgery prior to initiation of treatment. 17. Currently breastfeeding or pregnant. 18. There are circumstances that, i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Spleen size assessment;Myeloproliferative Neoplasm-SAF (MPN-SAF TSS) Assessment; | — |
Countries
China
Contacts
Public ContactXiao Zhijian
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Outcome results
None listed