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)

A 2-Part, Phase 2, Open-Label Study of the Safety, Tolerability, and Efficacy of Itacitinib Immediate Release in Participants With Primary Myelofibrosis or Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis) Who Have Received Prior Ruxolitinib and/or Fedratinib Monotherapy

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.

Study Overview

• Status: Completed
• Conditions: Polycythemia Vera; Myelofibrosis; Thrombocythemia
• Intervention / Treatment: Drug: itacitinib

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, 70376
    • Interne 1 - Hematologie Mit Stammzelltransplantation, Hemostaseologie Und Medizinische Onkologie Ord
• Belgium
  • Brussels, Belgium, 01000
    • Cliniques Universitaires Ucl Saint-Luc
  • Hasselt, Belgium, 03500
    • Jessa Ziekenhuis
  • Roeselare, Belgium, 08800
    • AZ Delta
  • Yvoir, Belgium, 05530
    • Chu Ucl Namur University Hospital Mont-Godinne
• Germany
  • Greifswald, Germany, 17475
    • Universitaetsmedizin Greifswald
  • Halle, Germany, 06120
    • Universitatsklinikum Halle (Saale)
• Italy
  • Milan, Italy, 20132
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
  • Salerno, Italy, 84131
    • Aou San Giovanni Di Dio E Ruggi
  • Treviso, Italy, 31100
    • Treviso Hospital
• Poland
  • Katowice, Poland, 40-519
    • Pratia Hematologia Katowice
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46000
    • Hospital Universitari i Politecnic La Fe
• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Rcca Md, Llc
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • MidAmerica Cancer Care
  • New Jersey
    • Brick, New Jersey, United States, 08724-3009
      • New Jersey Hematology Oncology Associates LLC
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Cancer Center
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75246-2092
      • Texas Oncology - Baylor Sammons Cancer Center
    • Spring, Texas, United States, 77380
      • Renovatio Clinical Consultants Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: itacitinib; itacitinb Immediate Release (IR) will be dosed orally twice a day; Other Names: INCB039110
Experimental: Part 2 : Dose Expansion of itacitinib; Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1.	Drug: itacitinib; itacitinb Immediate Release (IR) will be dosed orally twice a day; Other Names: INCB039110

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.	up to 724 days
Part 1: Number of Participants With Any Grade 3 or Higher TEAE	A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.	up to 724 days
Part 2: Splenic Response Rate (SRR) at Week 24	SRR was defined as the percentage of participants who had a reduction in spleen volume (by imaging) of at least 35% when compared with Baseline.	Baseline; Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Number of Participants With Any TEAE	An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.	up to at least 24 weeks
Part 2: Number of Participants With Any Grade 3 or Higher TEAE	A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.	up to at least 24 weeks
Part 2: Total Symptom Score (TSS) Response Rate at Week 24	TSS response was defined as the percentage of participants who achieved at least 50% reduction in TSS over the 28 days immediately before the end of Week 24 compared with the 7 days immediately before the initiation of itacitinib immediate release (aseline).B	Baseline; Week 24
Part 2: Mean Change (From Day 1 Versus 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)	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was to be used to assess the improvement in quality of life.	Baseline; Weeks 12 and 24
Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC)	The PGIC consists of a single question pertaining to a participant's overall status since the start of the study. The questionnaire gives participants 7 options to describe their overall status including: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse.	Baseline; Week 24

Collaborators and Investigators

• Sponsor: Incyte Corporation

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): August 24, 2023
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Myeloproliferative Neoplasms; Myelofibrosis; MF; Post-PV Myelofibrosis; Post-ET Myelofibrosis; LIMBER; LIMBER-213
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Bone Marrow Diseases; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Thrombocytosis; Polycythemia Vera; Primary Myelofibrosis; itacitinib; INCB039110
• Other Study ID Numbers: INCB 39110-213/LIMBER-213; 2020-003123-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No