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 (saale), 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 : Treatment Emergent Adverse Events (TEAE'S)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 30 days after last dose of study treatment.	24 Weeks
Part 2 : Spleen Volume Reduction by MRI/CT Scan	Defined as the proportion of participants who have a reduction in spleen volume (by imaging) of at least 35 percent when compared with baseline.	24 weeks
Part 2 : Spleen Volume Reduction	Defined as the proportion of participants who have a reduction in spleen volume (by imaging) of at least 35% when compared with baseline.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2 : Treatment Emergent Adverse Events (TEAE'S)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 30 days after last dose of study treatment.	13 months
Part 2 : Improvement in Total Symptom Score (TSS)	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 the initiation of itacitinib IR (baseline).	24 Weeks
Part 2 : Improvement in quality of life.	Defined as the mean change in the 5 multi-item functional scale scores and the multi-item global health status scale score (EORTC QLQ-C30).	24 weeks
Part 2 : Improvement in Patient Global Impression of Change (PGIC)	Defined as percentage of participants who are categorized as improved	24 Weeks

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 (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

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; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: INCB 39110-213/LIMBER-213

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