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)

• Status: Recruiting
• Trial end date: 2024-07-29
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Incyte Corporation

Criteria

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.