Clinical trial 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)
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelofibrosis
Polycythemia Vera
Thrombocythemia
Keywords: Myelofibrosis
Post-PV Myelofibrosis
Post-ET Myelofibrosis
LIMBER
LIMBER-213
MF
Myeloproliferative Neoplasms
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 724 days
measure: Part 1: Number of Participants With Any Grade 3 or Higher TEAE
timeFrame: up to 724 days
measure: Part 2: Splenic Response Rate (SRR) at Week 24
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Part 2: Number of Participants With Any TEAE
timeFrame: up to at least 24 weeks
measure: Part 2: Number of Participants With Any Grade 3 or Higher TEAE
timeFrame: up to at least 24 weeks
measure: Part 2: Total Symptom Score (TSS) Response Rate at Week 24
timeFrame: Baseline; Week 24
measure: 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)
timeFrame: Baseline; Weeks 12 and 24
measure: Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC)
timeFrame: Baseline; Week 24
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Bethesda
country: United States
facility: Rcca Md, Llc
state: Maryland
city: Kansas City
country: United States
facility: Midamerica Cancer Care
state: Missouri
city: Brick
country: United States
facility: New Jersey Hematology Oncology Associates Llc
state: New Jersey
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Spring
country: United States
facility: Renovatio Clinical Consultants Llc
state: Texas
city: Linz
country: Austria
facility: Interne 1 - Hematologie Mit Stammzelltransplantation, Hemostaseologie Und Medizinische Onkologie Ord
city: Brussels
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Roeselare
country: Belgium
facility: AZ DELTA
city: Yvoir
country: Belgium
facility: Chu Ucl Namur University Hospital Mont-Godinne
city: Greifswald
country: Germany
facility: Universitaetsmedizin Greifswald
city: Halle (saale)
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: Milan
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
city: Salerno
country: Italy
facility: Aou San Giovanni Di Dio E Ruggi
city: Treviso
country: Italy
facility: Treviso Hospital
city: Katowice
country: Poland
facility: Pratia Hematologia Katowice
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
Study officials:
References: