Myelofibrosis
Conditions
Interventions
phase IA:WJ01024 monotherapy
phase IB:WJ01024 combined with Ruxolitinib
Sponsors
Henan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Participants are voluntarily enrolled in this study after fully informed consent, and signed the informed consent form; 2. Age =18 years old, no gender limited; 3. A diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) classification, or a diagnosis of post ET myelofibrosis (PET-MF) or post PV myelofibrosis (PPV-MF) according to the International Working Group on Myelofibrosis Research and Treatment (IWG-MRT) classification, with or without JAK2 mutation; 4. Participants with DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk; 5. Life expectancy of greater than 24 weeks; 6. Eastern Cooperative Oncology Group (ECOG) score =2; 7. Participants currently not eligible for stem cell transplantation; 8. Splenomegaly: measurable splenomegaly as demonstrated by palpation of the splenic edge reaching to or exceeds at least 5cm below the costal margin (the distance from the costal edge to the farthest point of spleen), or spleen volume of =450 cm3 by magnetic resonance imaging (MRI) or computerized tomography (CT) scan; 9. Adequate function of vital organs, and laboratory tests performed within 7 days prior to the first dose of the investigational product (without need for blood transfusion, growth factors, colony-stimulating factors, platelet production factors, and platelet transfusion within 14 days before the tests), including : • Absolute neutrophil count (ANC) =1.5×109/L; • Stage IA: platelets =75×109/L; Stage IB: platelets =100×109/L; • Hemoglobin(HgB) =8.0 g/dL; • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =3.0×ULN; • Total bilirubin =1.5×ULN; • Serum creatinine =1.5×ULN. 10. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of WJ01024 and agree to use highly effective methods of contraception throughout the WJ01024 treatment period and for 90 days following the last dose of WJ01024 treatment. Male participants with a sexual partner who is a woman of reproductive age must agree to use an effective contraceptive method throughout the WJ01024 treatment period and for 90 days following the last dose of WJ01024 treatment. Special inclusion criteria: 11. Stage IA: previous treatment with JAK inhibitors for at least 3 months if JAK inhibitors are tolerated; 12. Stage IA: Relapsed, Refractory or Intolerant to JAK inhibitors as defined as meeting one of the criteria below: •25% from nadir or a return to within 10% of baseline after any initial response or •Treatment with JAK inhibitors was complicated by development of red blood cells (RBC) transfusion requirement (2 units per month for 2 month); or grade 3 thrombocytopenia, anemia, hematoma/hemorrhage; or grade 2 non-hematologic toxicity while on JAK inhibitors; 13. Stage IB: participants who have not received JAK inhibitors treatment in the past or who have been treated with JAK inhibitors for less than 14 days; 14. Stage IA and IB: =5% blasts in peripheral blood or =10% blasts in bone marrow.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded: 1. General conditions: 1) Pregnant or lactating women; 2) Any known allergies or contraindications to components of the study drug; 3) History of drug abuse; 4) History of alcohol abuse or consumption of more than 28 units of alcohol per week (1 unit =285ml beer or 25ml spirits (40%v/v) or 100ml wine). 2. Previous or current treatment: 1) Previous or current XPO-1 inhibitor treatment; 2) Unable or unwilling to undergo MRI/CT scan; 3) History of organ transplant or stem cell transplant; major surgery or major trauma (excluding needle biopsy for sample collection) within 4 weeks prior to the first administration of study drug; 4) Received investigational drugs or medical devices within 4 weeks prior to enrollment; 5) Received hydroxyurea treatment within 2 weeks prior to the first administration of WJ01024; 6) Received anti-myelofibrosis treatment (except JAK inhibitors and hydroxyurea), immunomodulator (e.g. thalidomide, interferon), immunosuppressive agent, >10mg/day prednisone or other glucocorticoids of equivalent biological strength within 2 weeks before the first administration of WJ01024, or within 5 half-lives of drugs mentioned above, whichever is longer (applicable to stage IA); 7) Receiving anti-myelofibrosis treatment (except JAK inhibitors and hydroxyurea), and a stable regimen (dose and frequency) cannot last for at least 2 weeks prior to screening; if the investigator considers that there is no need for further treatment, current treatment cannot be discontinued at screening; drugs for improving anemia, such as thalidomide, androgens, and >10mg prednisone, cannot be discontinued for at least 5 half-lives or 2 weeks (whichever is longer) before the first administration of WJ01024) (applicable to Phase IB); 8) Allergic to ruxolitinib or JAK inhibitors (Applicable to Phase IB); 9) Received strong CYP3A inhibitors or inducers within 14 days before the first administration of WJ01024; 3. Medical history and abnormal laboratory indicators: 1) Having active GI abnormalities including, but not limited to, inability to take oral medication, need for intravenous nutritional support, peptic ulcer, chronic diarrhea (e.g., Crohn's disease, irritable bowel syndrome), or vomiting or other factors that the investigator believes may significantly affect drug absorption, metabolism, or excretion; 2) Severe or poorly controlled hypertension, including previous history of hypertensive crisis or hypertensive encephalopathy; adjustment of antihypertensive medication due to poor blood pressure control within 2 weeks before the first dose; systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg during the screening period; 3) History of other primary solid tumors (except: cured solid tumors with no activity for =5 years before screening and have a low risk of recurrence; adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of recurrence; adequately treated carcinoma in situ with no evidence of recurrence, e.g. cervical carcinoma in situ); 4) History of active tuberculosis infection, or a positive tuberculosis test (such as gamma interferon release test) during screening with confirmation of active tuberculosis infection by investigator (applicable to Phase IB); 5) Clinical symptoms of bacterial, viral, parasitic or fungal infection that require treatment during screening (applicable to stage IB); 6) History of cardiac diseases: New York He
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicity (DLT), incidence and severity of adverse events (AEs) and serious adverse events (SAEs), abnormal laboratory tests and other tests that are clinically significant;MTD and RP2D; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in Splenic Volume;Pharmacokinetic parameters;Percentage of participants with Spleen Volume Reduction of >= 35% (SVR35) based on investigator’s assessment;Percentage of participants with Spleen Volume Reduction of >= 25% (SVR25) based on investigator’s assessment;Duration of SVR35 and SVR25 based on investigator’s assessment;Percentage of participants with TSS reduction of >= 50% (TSS50) in the Myeloproliferative Neoplasms Total Symptom Assessment Scale (MPN-SAF-TSS) based on investigator’s assessment;Anaemia response in participants as per International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria based on investigator’s assessment;Overall Response Rate (ORR) as per IWG-MRT based on investigator’s assessment;Leukemia-free survival (LFS) based on investigator’s assessment;Progression-free survival (PFS) based on investigator’s assessment;Changes in serum LDH level;Changes in transfusion needs;Changes in mutations of myeloid tumors ;Overall survival (OS); | — |
Countries
China
Contacts
Public ContactZhou Hu
Henan Cancer Hospital
Outcome results
None listed