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)

NCT04629508 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: INCB 39110-213/LIMBER-2132020-003123-42
• Study Type: interventional
• Target: 4
• Locations: 7 countries
• Sites: 21

Brief 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.

Conditions

Myelofibrosis; Polycythemia Vera; Thrombocythemia

Keywords

Myelofibrosis; Post-PV Myelofibrosis; Post-ET Myelofibrosis; LIMBER; LIMBER-213; MF; Myeloproliferative Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Part 2: Number of Participants With Any TEAE

  up to at least 24 weeks

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

  up to at least 24 weeks

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

  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)

  Baseline; Weeks 12 and 24

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

  Baseline; Week 24

Study Arms (2)

Part 1 : Dose Escalation of itacitinib

EXPERIMENTAL

Participants will be dosed at different dose levels with a maximum of up to 9 participants per dose level.

Drug: itacitinib

Part 2 : Dose Expansion of itacitinib

EXPERIMENTAL

Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1.

Drug: itacitinib

Interventions

itacitinib DRUG

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

Also known as: INCB039110

Part 1 : Dose Escalation of itacitinib; Part 2 : Dose Expansion of itacitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (21)

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Rcca Md, Llc

Bethesda, Maryland, 20817, United States

Location

Midamerica Cancer Care

Kansas City, Missouri, 64114, United States

Location

New Jersey Hematology Oncology Associates Llc

Brick, New Jersey, 08724-3009, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, 75246-2092, United States

Location

Renovatio Clinical Consultants Llc

Spring, Texas, 77380, United States

Location

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

Linz, 70376, Austria

Location

Cliniques Universitaires Ucl Saint-Luc

Brussels, 01000, Belgium

Location

Jessa Ziekenhuis

Hasselt, 03500, Belgium

Location

AZ DELTA

Roeselare, 08800, Belgium

Location

Chu Ucl Namur University Hospital Mont-Godinne

Yvoir, 05530, Belgium

Location

Universitaetsmedizin Greifswald

Greifswald, 17475, Germany

Location

Universitatsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele

Milan, 20132, Italy

Location

Aou San Giovanni Di Dio E Ruggi

Salerno, 84131, Italy

Location

Treviso Hospital

Treviso, 31100, Italy

Location

Pratia Hematologia Katowice

Katowice, 40-519, Poland

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitari I Politecnic La Fe

Valencia, 46000, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera; Thrombocytosis; Myeloproliferative Disorders

Interventions

itacitinib; INCB039110

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Platelet Disorders

Limitations and Caveats

The sponsor terminated study enrollment following an assessment regarding the expected duration of recruitment for the Phase 2 portion of the study combined with the availability of other study options for this patient population.

Results Point of Contact

• Title: Study Director
• Organization: 1-855-463-3463

medinfo@incyte.com

1-855-463-3463

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 16, 2020
• Study Start: July 12, 2021
• Primary Completion: August 24, 2023
• Study Completion: August 24, 2023
• Last Updated: September 2, 2025
• Results First Posted: September 19, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.

Locations

US (8); AU (1); BE (4); DE (2); IT (3); PL (1); ES (2)