Intermediate- to High-Risk Myelofibrosis, Polycythemia Vera, and Essential Thrombocythemia
Conditions
Interventions
Myelofibrosis (MF) (dose escalation):Bids, po, 8mg
Myelofibrosis (MF) (dose escalation):Bids, po, 16mg
Myelofibrosis (MF) (dose escalation):Bids, po, 24mg
Myelofibrosis (MF) (dose escalation):Bids, po, 32mg
Myelofibrosis (MF)(Dose Expansion):Bids, po, 8mg
Myelofibrosis (MF) (Dose Expansion):Bids, po, 16mg
Myelofibrosis (MF) (Dose Expansion):Bids, po, 20mg
Polycythemia Vera (PV):Bids, po, 16mg
Polycythemia Vera (PV):Bids, po, 20mg
Essential Thrombocythemia (ET):Bids, po, 16mg
Essential Thrombocythemia (ET):Bids, po, 20mg
Sponsors
The First Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1, Age >=18 years, male or female. 2, Diagnosis of Primary Myelofibrosis (PMF), Polycythemia Vera (PV), or Essential Thrombocythemia (ET) according to the 2016 WHO criteria; OR diagnosis of Post-PV Myelofibrosis (Post-PV-MF) or Post-ET Myelofibrosis (Post-ET-MF) according to IWG-MRT criteria. 3, MF Patients: Dose Escalation: Must be Intermediate-2 risk or higher according to the International Prognostic Scoring System (IPSS) (with >=1 adverse prognostic factor), have received at least one prior therapy, and have unsatisfactory response to current available therapies OR be deemed unsuitable for existing therapies by the investigator. Dose Expansion: Must be Intermediate-1 risk or higher according to IPSS (with >=1 adverse prognostic factor). Cohort A: MF patients naive to ruxolitinib treatment. Cohort B: MF patients with prior ruxolitinib failure or intolerance: Ruxolitinib Intolerance:Previous or current ruxolitinib treatment (>=28 days) AND: a. Required red blood cell transfusions during ruxolitinib treatment, OR b. Ruxolitinib dose (including starting or adjusted dose) =3 months AND met >=1 of the following: a. No significant reduction in spleen volume, OR b. >=10% increase in spleen volume by MRI/CT compared to nadir during treatment OR >=30% increase by palpation. 4, Dose Expansion - PV Patients: Must meet criterion a and/or b: a. HU-Resistant or Intolerant PV: Meet >=1 of the following: HU Resistance: Required phlebotomy to maintain Hct=2 g/day for >=3 months. Failure to control myeloproliferation (e.g., PLT>400×10?/L AND WBC>10×10?/L) despite HU >=2 g/day for >=3 months. Failure to achieve >50% spleen size reduction despite HU >=2 g/day for >=3 months. HU Intolerance: ANC 1 week, OR leading to permanent IFN-a discontinuation, OR requiring interruption until resolution, OR hospitalization due to IFN-a toxicity. 5, Dose Expansion - ET Patients: Must meet criterion a and/or b: a. HU-Resistant or Intolerant ET: Meet >=1 of the following: PLT >600×10?/L after =3 months of HU therapy at >=2 g/day (or >=2.5 g/day if body weight >80 kg) OR at maximum tolerated dose 400×10?/L AND WBC 400×10?/L AND HGB =24 weeks. 7, ECOG performance status 0-2. 8, Dose Expansion MF: Palpable splenomegaly >=5 cm below the le
Exclusion criteria
Exclusion criteria: 1, Major surgery within 4 weeks prior to screening and not fully recovered. 2, Prior splenectomy OR splenic irradiation within 3 months prior to screening. 3, History of seizures OR use of antipsychotics/sedatives at screening. 4, Prior/concomitant therapy restrictions: MF: Any MF-directed therapy within 2 weeks prior to enrollment, including chemotherapy, immunomodulatory therapy (e.g., thalidomide, interferon-a), immunosuppressive therapy (e.g., >10 mg/day prednisone or equivalent corticosteroids), radiotherapy, erythropoietin, androgens, thrombopoietin, or G-CSF. Exception for Dose Escalation: Stable-dose hydroxyurea (HU) for >=4 weeks is allowed, provided the dose does not exceed the stable dose used for blood count control. PV/ET: Any PV/ET-directed therapy within 1 week prior to enrollment. Acetylsalicylic acid (aspirin) 480 ms. 7, Active, clinically significant bacterial, viral, parasitic, or fungal infection requiring systemic therapy at screening. 8, History of other malignancy within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ of the breast treated surgically with curative intent, localized prostate cancer (T1a or T1b by TNM staging), or thyroid cancer treated surgically with curative intent. 9, Persistent toxicity =Grade 2 from prior anti-cancer therapy (except stable, non-resolving chronic toxicities such as peripheral neuropathy). 10, Any other severe concurrent medical condition that, in the investigator's judgment, makes the subject inappropriate for study participation. 11, Any significant clinical or laboratory abnormality that, in the investigator's opinion, may compromise safety assessment, including uncontrolled diabetes (requiring hospitalization or insulin), hypertension uncontrolled (SBP >150 mmHg or DBP >100 mmHg) on >=2 antihypertensive agents, thyroid dysfunction (>Grade 2 per NCI-CTCAE v5.0). 12, Known positive status at screening for: HIV antibody. HBsAg positive AND HBV DNA >=1000 copies/mL (or equivalent IU/mL). HCV antibody positive AND HCV RNA positive. 13, Known hypersensitivity to ruxolitinib or drugs of similar chemical structure. 14, Women who are pregnant, breastfeeding, planning to become pregnant, or men/women of childbearing potential unwilling to use highly effective contraception during the study and for a specified period after. 15, Participation in another investigational drug or device clinical trial within 4 weeks prior to the first dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects with a reduced spleen volume of =35% at 24 weeks accounted for all subjects; | — |
Secondary
| Measure | Time frame |
|---|---|
| p-STAT3 inhibition;Change in JAK2 Mutation Burden from Baseline at Weeks 24, 48, and the End of Treatment (EOT) Visit;Clinical Hematological Response Rate at Weeks 12, 24, 36, and 48;Plasma Concentration;Spleen Response: Defined as the proportion of patients achieving =35% reduction in spleen volume from baseline on at least one assessment.;Occurrence of adverse events; | — |
Countries
China
Contacts
Public ContactJie Jin
The First Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed