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)
- Conditions
- Polycythemia VeraThrombocythemiaMyelofibrosis
- Interventions
- Registration Number
- NCT04629508
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 : Dose Expansion of itacitinib itacitinib Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1. Part 1 : Dose Escalation of itacitinib itacitinib Participants will be dosed at different dose levels with a maximum of up to 9 participants per dose level.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) 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.
Part 1: Number of Participants With Any Grade 3 or Higher TEAE 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.
Part 2: Splenic Response Rate (SRR) at Week 24 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 Outcome Measures
Name Time Method Part 2: Number of Participants With Any TEAE 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.
Part 2: Number of Participants With Any Grade 3 or Higher TEAE 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.
Part 2: Total Symptom Score (TSS) Response Rate at Week 24 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
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 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.
Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC) 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.
Trial Locations
- Locations (21)
Treviso Hospital
🇮🇹Treviso, Italy
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
🇮🇹Milan, Italy
Cliniques Universitaires Ucl Saint-Luc
🇧🇪Brussels, Belgium
Pratia Hematologia Katowice
🇵🇱Katowice, Poland
Midamerica Cancer Care
🇺🇸Kansas City, Missouri, United States
Texas Oncology - Baylor Sammons Cancer Center
🇺🇸Dallas, Texas, United States
New Jersey Hematology Oncology Associates Llc
🇺🇸Brick, New Jersey, United States
Renovatio Clinical Consultants Llc
🇺🇸Spring, Texas, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
AZ DELTA
🇧🇪Roeselare, Belgium
Universitatsklinikum Halle (Saale)
🇩🇪Halle (saale), Germany
Chu Ucl Namur University Hospital Mont-Godinne
🇧🇪Yvoir, Belgium
Rcca Md, Llc
🇺🇸Bethesda, Maryland, United States
Interne 1 - Hematologie Mit Stammzelltransplantation, Hemostaseologie Und Medizinische Onkologie Ord
🇦🇹Linz, Austria
Tulane University
🇺🇸New Orleans, Louisiana, United States
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
Aou San Giovanni Di Dio E Ruggi
🇮🇹Salerno, Italy
Universitaetsmedizin Greifswald
🇩🇪Greifswald, Germany
Hospital Universitari I Politecnic La Fe
🇪🇸Valencia, Spain