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)

Incyte

Status and phase: Completed; Phase 2

Conditions: Myelofibrosis; Thrombocythemia; Polycythemia Vera

Treatments: Drug: itacitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04629508

INCB 39110-213/LIMBER-213

2020-003123-42 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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4 participants in 2 patient groups

Part 1 : Dose Escalation of itacitinib

Experimental group

Description:

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

Treatment:

Drug: itacitinib

Part 2 : Dose Expansion of itacitinib

Experimental group

Description:

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

Treatment:

Drug: itacitinib