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)

Sponsor

Incyte Corporation (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04629508

Collaborator

(none)

Enrollment

Locations

Arms

36.6

Anticipated Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis Polycythemia Vera Thrombocythemia	Drug: itacitinib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 12, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Jul 29, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Part 1 : Treatment Emergent Adverse Events (TEAE'S) [24 Weeks]
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 [24 weeks]
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 [24 weeks]
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) [13 months]
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) [24 Weeks]
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. [24 weeks]
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) [24 Weeks]
Defined as percentage of participants who are categorized as improved

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

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