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Completed

NCT Number: NCT04629508

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)

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.

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Key information

Conditions

Myelofibrosis Blood Platelet Disorders Bone Marrow Diseases Bone Marrow Neoplasms Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Site Polycythemia Vera Primary Myelofibrosis Thrombocythemia Thrombocytosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Interne 1 - Hematologie Mit Stammzelltransplantation, Hemostaseologie Und Medizinische Onkologie Ord, Linz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Itacitinib

Drug

itacitinb Immediate Release (IR) will be dosed orally twice a day

Other names: INCB039110

Primary outcomes

  1. Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

    Time frame: up to 724 days

    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.

  2. Part 1: Number of Participants With Any Grade 3 or Higher TEAE

    Time frame: up to 724 days

    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.

  3. Part 2: Splenic Response Rate (SRR) at Week 24

    Time frame: Baseline; 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.

Secondary outcomes

  1. Part 2: Number of Participants With Any TEAE

    Time frame: up to at least 24 weeks

    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.

  2. Part 2: Number of Participants With Any Grade 3 or Higher TEAE

    Time frame: up to at least 24 weeks

    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.

  3. Part 2: Total Symptom Score (TSS) Response Rate at Week 24

    Time frame: Baseline; 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

  4. 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)

    Time frame: Baseline; Weeks 12 and 24

    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.

  5. Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC)

    Time frame: Baseline; Week 24

    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.

Sponsors and collaborators

Lead sponsor

Incyte Corporation

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Nov 16, 2020
Registry last updated
Sep 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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