Myelofibrosis MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10074689 Term: Post polycythemia vera myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10074690 Term: Post essential thrombocythemia mye
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort A only • Receiving ruxolitinib dose of less than 20 mg daily with no dose increase or no dose modification in the last 8 weeks before screening visit. Cohort B only • Must have had initial reduction in spleen on ruxolitinib treatment (response is defined by any spleen length or volume reduction, by palpation or MRI/CT assessment, from baseline while on previous ruxolitinib treatment per IWG-MRT ELN 2013 guidelines): - Followed by documented evidence of progression in spleen length or volume OR - Discontinued ruxolitinib for hematologic toxicities, after the initial reduction in spleen length or volume. All subjects • Men and women, aged 18 years or older. • Confirmed diagnosis of PMF, PPV-MF, or PET-MF according to revised WHO 2016 criteria. • Must have palpable spleen of = 5 cm below the left subcostal margin on physical examination at the screening visit. (If spleen is not palpable due to body habitus, spleen enlargement must be documented by other means [eg, ultrasound or MRI] and study sponsor medical monitor be contacted for acceptance). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: All subjects • Lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better. • Previous treatment with itacitinib or JAK1 inhibitors (JAK1/JAK2 inhibitor ruxolitinib is permitted).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate preliminary efficacy of itacitinib (INCB039110) on spleen volume reduction (SVR) from baseline at Week 24 in the 2 following cohorts of MF subjects: • Cohort A: in combination in subjects with ruxolitinib low dose (less than 20mg daily). • Cohort B: as monotherapy in subjects who progressed (per revised European LeukemiaNet [ELN] 2013 response criteria for MF) after initial reduction in spleen on ruxolitinib or discontinued for hematologic toxicities.;Secondary Objective: - To evaluate preliminary safety and tolerability of itacitinib alone. - To evaluate preliminary safety and tolerability of itacitinib in combination with ruxolitinib. - To evaluate preliminary efficacy of itacitinib alone or in combination with ruxolitinib on SVR from baseline at Week 12. - To evaluate preliminary efficacy of itacitinib alone or in combination with ruxolitinib on spleen length reduction from baseline at Week 12 and Week 24. - To evaluate preliminary efficacy of itacitinib alone or in combination with ruxolitinib with respect to MF symptoms at Week 12 and Week 24. - To evaluate preliminary efficacy of itacitinib using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. - To assess the pharmacokinetics (PK) of itacitinib and ruxolitinib.;Primary end point(s): Change and percentage change in SVR as measured by magnetic resonance imaging [MRI] (computed tomography [CT] scan in subjects who are not candidates for MRI or when MRI is not readily available) at Week 24 when compared with baseline.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety and tolerability through assessment of frequency, severity, and duration of AEs; changes in clinical safety assessments; and changes in clinical laboratory parameters. - Change and percentage in SVR from baseline through Week 12 as measured by MRI (or CT scan in applicable subjects). - Change and percentage change on spleen length reduction from baseline through Week 12 and Week 24 as measured by palpation. - Change and percentage change in TSS from baseline through Week 12 and Week 24 as measured by the MFSAF v2.0 symptom diary and by the MPN-SAF. - PGIC score at each visit where the variable is measured. - Number of subjects with responses according to the 2013 IWG-MRT consensus criteria for treatment response. - Calculation of the PK parameters such as AUC, CL/F, Cmax, and tmax along with summarization of the observed concentration data by timepoint will be performed for both ruxolitinib and itacitinib.;Timepoint(s) of evaluation of this end point: Adverse events will be monitored from the time the subject signs the ICF through the safety follow-up. From baseline through Week 12 From baseline through Week 12 and Week 24 PK: Week 2 and Week 4 | — |
Countries
Austria, Netherlands, Switzerland, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed