Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
INCB 39110-213/LIMBER-213
- NCT ID:
NCT04821791
Conditions
- Myelofibrosis
- Polycythemia Vera
- Thrombocythemia
Interventions
| Drug | Synonyms | Arms |
|---|
| itacitinib | INCB039110 | Part 1 : Dose Escalation of itacitinib |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | |
| Part 2 : Dose Expansion of itacitinib | Experimental | Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1. | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1 : Treatment Emergent Adverse Events (TEAE'S) |
| Time Frame: | 24 Weeks |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | Part 2 : Treatment Emergent Adverse Events (TEAE'S) |
| Time Frame: | 13 months |
| Safety Issue: | |
| 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. |
| Measure: | Part 2 : Improvement in Total Symptom Score (TSS) |
| Time Frame: | 24 Weeks |
| Safety Issue: | |
| Description: | Defined as the proportion of participants who achieve at least 50 percent 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). |
| Measure: | Part 2 : Improvement in quality of life. |
| Time Frame: | 24 weeks |
| Safety Issue: | |
| 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). |
| Measure: | Part 2 : Improvement in Patient Global Impression of Change (PGIC) |
| Time Frame: | 24 Weeks |
| Safety Issue: | |
| Description: | Defined as percentage of participants who are categorized as improved |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Incyte Corporation |
Trial Keywords
- Myelofibrosis
- Post-PV Myelofibrosis
- Post-ET Myelofibrosis
- LIMBER
- LIMBER-213
- MF
- Myeloproliferative Neoplasms
Last Updated
March 30, 2021
