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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)

Primary Purpose

Myelofibrosis, Polycythemia Vera, Thrombocythemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
itacitinib
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis, Post-PV Myelofibrosis, Post-ET Myelofibrosis, LIMBER, LIMBER-213, MF, Myeloproliferative Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Tulane University
  • Rcca Md, Llc
  • Midamerica Cancer Care
  • New Jersey Hematology Oncology Associates Llc
  • Baptist Cancer Center
  • Vanderbilt University
  • Texas Oncology - Baylor Sammons Cancer Center
  • Renovatio Clinical Consultants Llc
  • Interne 1 - Hematologie Mit Stammzelltransplantation, Hemostaseologie Und Medizinische Onkologie Ord
  • Cliniques Universitaires Ucl Saint-Luc
  • Jessa Ziekenhuis
  • AZ DELTA
  • Chu Ucl Namur University Hospital Mont-Godinne
  • Universitaetsmedizin Greifswald
  • Universitatsklinikum Halle (Saale)
  • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
  • Aou San Giovanni Di Dio E Ruggi
  • Treviso Hospital
  • Pratia Hematologia Katowice
  • Hospital Universitario 12 de Octubre
  • Hospital Universitari I Politecnic La Fe

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1 : Dose Escalation of itacitinib

Part 2 : Dose Expansion of itacitinib

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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).
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).
Part 2 : Improvement in Patient Global Impression of Change (PGIC)
Defined as percentage of participants who are categorized as improved

Full Information

First Posted
November 10, 2020
Last Updated
August 28, 2023
Sponsor
Incyte Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04629508
Brief Title
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)
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
July 12, 2021 (Actual)
Primary Completion Date
August 24, 2023 (Actual)
Study Completion Date
August 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis, Polycythemia Vera, Thrombocythemia
Keywords
Myelofibrosis, Post-PV Myelofibrosis, Post-ET Myelofibrosis, LIMBER, LIMBER-213, MF, Myeloproliferative Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 : Dose Escalation of itacitinib
Arm Type
Experimental
Arm Description
Participants will be dosed at different dose levels with a maximum of up to 9 participants per dose level.
Arm Title
Part 2 : Dose Expansion of itacitinib
Arm Type
Experimental
Arm Description
Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1.
Intervention Type
Drug
Intervention Name(s)
itacitinib
Other Intervention Name(s)
INCB039110
Intervention Description
itacitinb Immediate Release (IR) will be dosed orally twice a day
Primary Outcome Measure Information:
Title
Part 1 : Treatment Emergent Adverse Events (TEAE'S)
Description
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.
Time Frame
24 Weeks
Title
Part 2 : Spleen Volume Reduction by MRI/CT Scan
Description
Defined as the proportion of participants who have a reduction in spleen volume (by imaging) of at least 35 percent when compared with baseline.
Time Frame
24 weeks
Title
Part 2 : Spleen Volume Reduction
Description
Defined as the proportion of participants who have a reduction in spleen volume (by imaging) of at least 35% when compared with baseline.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Part 2 : Treatment Emergent Adverse Events (TEAE'S)
Description
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.
Time Frame
13 months
Title
Part 2 : Improvement in Total Symptom Score (TSS)
Description
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).
Time Frame
24 Weeks
Title
Part 2 : Improvement in quality of life.
Description
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).
Time Frame
24 weeks
Title
Part 2 : Improvement in Patient Global Impression of Change (PGIC)
Description
Defined as percentage of participants who are categorized as improved
Time Frame
24 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Tulane University
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Rcca Md, Llc
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Midamerica Cancer Care
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64114
Country
United States
Facility Name
New Jersey Hematology Oncology Associates Llc
City
Brick
State/Province
New Jersey
ZIP/Postal Code
08724-3009
Country
United States
Facility Name
Baptist Cancer Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37235
Country
United States
Facility Name
Texas Oncology - Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246-2092
Country
United States
Facility Name
Renovatio Clinical Consultants Llc
City
Spring
State/Province
Texas
ZIP/Postal Code
77380
Country
United States
Facility Name
Interne 1 - Hematologie Mit Stammzelltransplantation, Hemostaseologie Und Medizinische Onkologie Ord
City
Linz
ZIP/Postal Code
70376
Country
Austria
Facility Name
Cliniques Universitaires Ucl Saint-Luc
City
Brussels
ZIP/Postal Code
01000
Country
Belgium
Facility Name
Jessa Ziekenhuis
City
Hasselt
ZIP/Postal Code
03500
Country
Belgium
Facility Name
AZ DELTA
City
Roeselare
ZIP/Postal Code
08800
Country
Belgium
Facility Name
Chu Ucl Namur University Hospital Mont-Godinne
City
Yvoir
ZIP/Postal Code
05530
Country
Belgium
Facility Name
Universitaetsmedizin Greifswald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Universitatsklinikum Halle (Saale)
City
Halle (saale)
ZIP/Postal Code
06120
Country
Germany
Facility Name
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Facility Name
Aou San Giovanni Di Dio E Ruggi
City
Salerno
ZIP/Postal Code
84131
Country
Italy
Facility Name
Treviso Hospital
City
Treviso
ZIP/Postal Code
31100
Country
Italy
Facility Name
Pratia Hematologia Katowice
City
Katowice
ZIP/Postal Code
40-519
Country
Poland
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitari I Politecnic La Fe
City
Valencia
ZIP/Postal Code
46000
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.incyte.com/our-company/compliance-and-transparency
Links:
URL
https://www.incyteclinicaltrials.com/limber/
Description
Related Info

Learn more about this trial

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)

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