Primary Myelofibrosis or Secondary 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)
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 years or older at the time of signing the informed consent 2. Diagnosis of primary MF meeting the 2016 WHO criteria for overt PMF or secondary MF (PPV-MF or PET-MF) meeting the 2008 IWG-MRT criteria. 3. At least Intermediate 1 risk MF according to the DIPSS. 4. Prior treatment with ruxolitinib and/or fedratinib monotherapy: a. Previously treated with ruxolitinib and/or fedratinib monotherapy for PMF or secondary MF for not more than 6 months if treatment was discontinued due to recurrent Grade 4 thrombocytopenia; = Grade 3 anemia, hemorrhage, or hematoma; or allergy/other intolerance to ruxolitinib or fedratinib OR b. Currently receiving ruxolitinib or fedratinib monotherapy for PMF or secondary MF: - For at least 3 months with initial response but regrowth of spleen on imaging or by palpation compared with baseline; OR - For at least 28 days if treatment is complicated by recurrent Grade 4 thrombocytopenia; = Grade 3 anemia, hemorrhage, or hematoma; or allergy/other intolerance to ruxolitinib or fedratinib. 5. Splenomegaly defined as palpable spleen at least 5 cm below the left costal margin or volume = 450 cm3 on imaging assessed during screening. 6. Allogeneic stem cell transplant not planned. 7. Platelet = 50 × 109/L at screening. 8. Ability to comprehend and willingness to sign a written ICF for the study. 9. Willingness to avoid pregnancy or fathering children 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 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: 1. Prior treatment with a JAK inhibitor other than ruxolitinib or fedratinib 2. Record of = 10% myeloid blasts in the peripheral blood (on peripheral blood smear) or bone marrow prior to or at the time of screening 3. For participants on ruxolitinib or fedratinib, unable to be tapered from that treatment over the course of 14 days without corticosteroids, hydroxyurea, or other agents 4. Treatment with ruxolitinib, fedratinib or other MF-directed therapy (approved or investigational) within 2 weeks of Day 1 5. Prior splenectomy or splenic irradiation within 6 months before receiving the first dose of itacitinib 6. Unable or unwilling to undergo serial MRI or CT scans for spleen volume measurement 7. Unable or unwilling to complete MFSAF v4.0 diary on a daily basis during the study 8. ECOG performance status = 3 9. Life expectancy less than 24 weeks 10. Not willing to receive RBC or platelet transfusions 11. Participants with laboratory values at screening defined in Table 11 of protocol 12. Significant concurrent, uncontrolled medical condition, including but not limited to the following: Gastrointestinal, Cardiovascular 13. History or presence of an abnormal ECG that, in the investigator’s opinion, is clinically meaningful according to the guidance provided in Section 8.3.4 of the protocol. 14. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. 15. Hepatitis: Evidence of HBV or HCV infection or risk of reactivation. 16. Known HIV infection. 17. Current use of prohibited medication as described in Section 6.6.9 of protocol. 18. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator. 19. Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy. 20. Women who are pregnant or breastfeeding. 21. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of itacitinib IR and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. 22. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including: inability to self-administer itacitinib IR; difficulty attending required study visits; a comorbid condition that poses a significant risk to the participant or may interfere with interpretation of study data. 23. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To evaluate the safety and tolerability of itacitinib IR and select the RP2D for Part 2 of the study. Part 2: To evaluate the efficacy of itacitinib IR at the RP2D with respect to spleen volume reduction at Week 24.;Secondary Objective: Part 2: - To evaluate the safety and tolerability of itacitinib IR at the RP2D. - To evaluate the efficacy of itacitinib IR at the RP2D with respect to MF symptom improvement at Week 24, in those patients with a baseline TSS = 10. - To evaluate the efficacy of itacitinib IR with respect to improvement of quality of life. - To evaluate the efficacy of itacitinib IR at the RP2D with respect to PGIC.;Primary end point(s): Part 1: Safety and tolerability through assessments of frequency and severity of AEs; changes in clinical safety assessments; changes in clinical laboratory parameters. Part 2: SRR at Week 24, where SRR is defined as the proportion of participants who have a reduction in spleen volume (by imaging) of at least 35% 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 assessments of frequency and severity of AEs; changes in clinical safety assessments; changes in clinical laboratory parameters. TSS response rate at Week 24, where TSS response is defined as the proportion of participants who achieve at least 50% reduction in TSS over the 28 days immediately before the end of Week 24 compared with the 7 days immediately before initiation of itacitinib IR (baseline). The mean change (from Day 1 vs Week 12 and Week 24) in the 5 multi-item functional scale scores and the multi-item global health status scale score (EORTC QLQ-C30). ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Countries
Austria, Belgium, France, Germany, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed