splanchnic vein thrombosis associated with myeloproliferative neoplasm MedDRA version: 15.0 Level: LLT Classification code 10013238 Term: Disorder myeloproliferative System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Jakafy
Pharmaceutical Form: Tablet
INN or Proposed INN: RUXOLITINIB
CAS Number: 1092939-17-7
Current Sponsor code: INC424
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
UNIVERSITA' DEGLI STUDI DI FIRENZE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Study patient population is represented by male or female subjects with splanchnic vein thrombosis (SVT) (including Budd-Chiari syndrome, mesenteric vein thrombosis, portal vein thrombosis, splenic vein thrombosis) in the setting of myeloproliferative neoplasms, ie polycythemia vera (PV), essential thrombocythemia (ET) (according to the WHO criteria), or myelofibrosis both primary (PMF) and secondary to polycythemia vera (PPV-MF) or essential thrombocythemia (PET-MF) (according to the WHO and IWG-MRT criteria, respectively), either JAK2V617F positive or negative, MPLW515L/K positive or negative, who are equal to or older than 18 and have a palpable spleen greater than 5 cm from the costal margin to the point of greatest splenic protrusion, with a platelet count >100x109/L and normal liver function. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: 1.ALT or AST > 2.5 x ULN 2.Total bilirubin >2xULN 3.Active acute or chronic hepatitis A, B or C (Appendix III) 4.Presence of refractory ascites. 5.Presence of esophageal varices greater than grade 2 and/or a history of previous recurrent bleedings from varices, ie more than two episodes in the last 12 months. 6.Presence of TIPS (transjugular portosystemic shunt). 7.Creatinine level not greater than 1.5-fold the upper limit. 8.Other neoplastic disorders unless at least 3 years before and in complete remission except for treated, early-stage squamous or basal cell carcinoma of the skin. 9.Patient has hypersensitivity to Ruxolitinib or any of the eccipients. 10.Subjects with a life expectancy of less than 6 months 11.Subjects with inadequate bone marrow reserve as demonstrated by: •Absolute neutrophil count (ANC) that is = 1x109/L •Platelet count that is < 100x109/L without the assistance of growth factors, thrombopoietic factors or platelet transfusions. 12.Patient has a percentage of blast cell in peripheral blood greater than 5% within 14 days before enrollment. 13.Subjects with any history of platelet counts < 50x109/L or ANC < 0.5x109/L except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason. 14.Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy, except for antiviral prophylaxis: subjects with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 15.Subjects HIV-positive. 16.Patients undergoing treatment with hematopoietic growth factor receptor-agonists (i.e., erythropoietin [Epo], granulocyte colony stimulating factor (GCSF, romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or 4 weeks prior to baseline. 17.Patients receiving any medications listed in the “prohibited medications” listing 18.Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 19.Patients receiving ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of study drug treatment. 20.Patient is currently eligible, has the option, and is willing to undergo stem cell transplantation. 21.Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 22.Subjects with cardiac disease which in the Investigator’s opinion may jeopardize the safety of the subject or the compliance with the protocol. 23.Subjects with currently uncontrolled or unstable angina. 24.Subjects with currently rapid or paroxysmal atrial fibrillation. 25.Subjects who have had splenic irradiation within 12 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary goal of this study is to evaluate the efficacy of Ruxolitinib in patients with splenomegaly due to an underlying myeloproliferative neoplasms associated with splanchnic vein thrombosis.;Secondary Objective: The secondary objectives include the evaluation of safety of Ruxolitinib and QoL in this setting of patients, the assessment of a potential role of Ruxolitinib in splanchnic circulation;Primary end point(s): The proportion of subjects achieving = 50% reduction in spleen length at any time from baseline to week 24 and at week 24 as measured by palpation or = 35% reduction in spleen volume by MRI (or CT for subjects unable to undergo MRI) at week 24.;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 To evaluate the safety of Ruxolitinib in patients with MPN-associated SVT through: a.Changes from baseline through end of treatment in physical examinations, heart rate/rhythm, blood pressure, respiratory rate, and clinical laboratory findings. b.The observation and report of any AEs (including laboratory abnormalities reported as AEs)that occur between the first study related procedure through 28 days following the last dose of investigational product administration. The intensity (severity) of AEs will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. 2 To assess ability of Ruxolitinib to improve at least one of these findings at week 24. a.Splanchnic circulation, on portal, splenic and/or mesenteric vein. b.Hyperdynamic arterial circulation; c.Stiffnes of epathic/splenic parenchyma. 3 To determine the effects of the treatment on the capacity of Ruxolitinib to induce a clinico-hematological response according to ELN criteria for Polycythemia Vera and Essential Thombocythemia and IWG-MRT criteria for Myelofibrosis. 4 To evaluate change and improvement in QoL by use of Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) questionnaire response from Baseline at monthly interval.;Timepoint(s) of evaluation of this end point: week 2,4,6,8 and every 4 weeks thereafter, until Week 24. | — |
Countries
Italy
Contacts
Public ContactLab epid clinica malattie cardiovas
CONSORZIO MARIO NEGRI SUD
Outcome results
None listed