To Assess the Safety, Tolerability and Efficacy of Itacitinib Immediate Release Tablets in Participants With Primary or Secondary Myelofibrosis Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy (LIMBER-213)
Purpose
This is a 2-part study. In Part 1, participants will be dosed at 2 different dose levels in order to select the RP2D for Part 2 of the study.
Conditions
- Myelofibrosis
- Polycythemia Vera
- Thrombocythemia
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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. - At least Intermediate 1 risk MF according to the DIPSS. - Prior treatment with ruxolitinib and/or fedratinib monotherapy - Currently receiving ruxolitinib or fedratinib monotherapy for PMF or secondary MF. - Splenomegaly defined as palpable spleen at least 5 cm below the left costal margin or volume ≥ 450 cm3 on imaging assessed during screening. - Allogeneic stem cell transplant not planned. - Platelet is greater than or equal to 50 × 109/L at screening. - Ability to comprehend and willingness to sign a written ICF for the study. - Willingness to avoid pregnancy or fathering children.
Exclusion Criteria
- Prior treatment with a JAK inhibitor other than ruxolitinib or fedratinib - Record of ≥ 10% myeloid blasts in the peripheral blood (on peripheral blood smear) or bone marrow prior to or at the time of screening - 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 - Treatment with ruxolitinib, fedratinib or other MF-directed therapy (approved or investigational) within 2 weeks of Day 1 - Prior splenectomy or splenic irradiation within 6 months before receiving the first dose of itacitinib - Unable or unwilling to undergo serial MRI or CT scans for spleen volume measurement - Unable or unwilling to complete MFSAF v4.0 diary on a daily basis during the study - ECOG performance status ≥ 3 - Life expectancy less than 24 weeks - Not willing to receive RBC or platelet transfusions - Participants with laboratory values at screening outside of protocol defined ranges - Significant concurrent, uncontrolled medical condition - Participants with impaired cardiac function or clinically significant cardiac disease unless approved by medical monitor/sponsor - History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful - Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. - Evidence of HBV or HCV infection or risk of reactivation - Known HIV infection.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1 : Dose Escalation of itacitinib |
Participants will be dosed at different dose levels with a maximum of up to 9 participants per dose level. |
|
|
Experimental Part 2 : Dose Expansion of itacitinib |
Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1. |
|
More Details
- Status
- Completed
- Sponsor
- Incyte Corporation