Study of the JAK Inhibitor Ruxolitinib Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia-Myelofibrosis (PET-MF)

A Phase Ib, Open-label, Dose-finding Study of the JAK Inhibitor INC424 Tablets Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-polycythemia Veramyelofibrosis (PPV-MF) or Post-essentialthrombocythemia-myelofibrosis (PET-MF) and Baseline Platelet Counts ≥50 x109/L and <100 x109/L (EXPAND)

This is a Phase IB, open-label, dose-finding study of the JAK 1 and 2 inhibitor ruxolitinib in patients with myelofibrosis (MF). The study consists of two periods: the core study period, comprising the dose escalation stage and the safety extension phase up to Week 24, then the extension study period beyond Week 24 and up to 3 years, to further characterize the safety and efficacy of ruxolitinib in this patient population. The dose escalation phase will enroll successive cohorts of patients who receive increasing doses of ruxolitinib until the maximum safe starting dose (MSSD) is determined. In the safety expansion phase, additional patients will be treated with ruxolitinib at the MSSD defined during dose escalation. The primary objective is to establish the MSSD of ruxolitinib in patients with MF and starting platelet counts < 100 x 10 ^9/L

Study Overview

• Status: Completed
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
• China
  • Beijing, China
  • Jiangsu
    • Nanjing, Jiangsu, China
  • Sichuan
    • Chengdu, Sichuan, China
  • Zhejiang
    • Hangzhou, Zhejiang, China
• France
  • Angers, France
  • Paris, France
  • Pierre-Benite, France
• Germany
  • Leipzig, Germany
• Italy
  • Firenze, Italy
  • Milano, Italy
  • Terni, Italy
• Netherlands
  • Rotterdam, Netherlands
• United Kingdom
  • Belfast, United Kingdom
  • London, United Kingdom
• United States
  • Florida
    • Winter Park, Florida, United States, 32789
  • Maryland
    • Baltimore, Maryland, United States, 21229
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Require treatment for MF and classified at least as intermediate risk level 1 defined by the International Working Group.
• Platelet count < 100x10 ^9/L at screening or at Study Day 1.

Exclusion Criteria:

• Received platelet transfusion within 14 days prior to Screening evaluations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stratum -1; Participants with baseline Platelet counts of 75-99 x10^9/L	Drug: Ruxolitinib; Starting dose of ruxolitinib for cohort 1 in dose escalation phase - 5mg twice a day (BID) Doses will be increased a total of approximately 5mg for successive dosing cohorts based on baseline platelet count; Other Names: INCB018424
Experimental: Stratum -2; Participants with baseline Platelet counts of 50-74 x10^9/L	Drug: Ruxolitinib; Starting dose of ruxolitinib for cohort 1 in dose escalation phase - 5mg twice a day (BID) Doses will be increased a total of approximately 5mg for successive dosing cohorts based on baseline platelet count; Other Names: INCB018424

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities	DLT was defined as the occurrence of any of the following treatment-related toxicities, occurring through Day 28: Any grade ≥ 2 hemorrhagic event ; Any grade thrombocytopenia requiring PLT transfusion; PLT count < 25x109/L*; Grade 4 neutropenia (absolute neutrophil count < 0.5x109/L)*; Grade ≥ 3 febrile neutropenia*; Grade ≥ 2 total serum bilirubin with coincident direct bilirubin ≥ 0.5 mg/dL; Grade 3 non-hematologic toxicity for ≥ 7 consecutive days; Grade 4 non-hematologic toxicity. In the dose escalation stage in the core study period, the starting does in both strata was 5mg bid. Successive cohorts of newly enrolled patients received increasing doses of ruxolitinib until the Maximum Safe Starting Dose (MSSD) was determined. Initially, only patients with PLT counts 75-99 x10^9/L (stratum 1) were allowed to be enrolled. Once safety was established in stratum 1 at the first 2 dose cohorts, eligible population was further expanded to patients with PLT counts 50-74 x10^9/L (stratum 2).	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAE's)	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	approximately 4 years
Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length	Participants achieving ≥ 50% reduction in palpable spleen length relative to study day 1 by treatment and stratum	24 weeks
Change in Spleen Length as Measure by Palpation Over Time	Defined as measurement of change in spleen length by palpation from baseline	Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092
PK- C Reactive Protein Levels by PK Quartile (AUC0-12)	To define the PK and C Reactive Protein relationship using PK Quartiles (AUC 0-12, ng*h/mL)	24 weeks
PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12)	To define the PK and Interleukin 1 Receptor Antagonist relationship relationship using PK Quartiles (AUC 0-12, ng*h/mL)	24 weeks
PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12)	To define the PK and Tissue Necrosis Factor Receptor 2 relationship using PK Quartiles (AUC 0-12, ng*h/mL)	24 weeks
AUC 0-Inf	Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity	0.25 to 0.75, 1 to 3, and 4 to 12 hours postdose on Day 1 and predose, 0.25 to 0.75 hours, and 1 to 3 hours postdose on Day 15, with a random sample on Days 29 and 57

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: Novartis
• Investigators: Study Director: Mark Jones, MD, Incyte Corporation

Publications and helpful links

General Publications

• Guglielmelli P, Kiladjian JJ, Vannucchi AM, Duan M, Meng H, Pan L, He G, Verstovsek S, Boyer F, Barraco F, Niederwieser D, Pungolino E, Liberati AM, Harrison C, Roussou P, Wroclawska M, Karumanchi D, Sinclair K, Te Boekhorst PAW, Gisslinger H. Efficacy and safety of ruxolitinib in patients with myelofibrosis and low platelet count (50 x 109/L to <100 x 109/L) at baseline: the final analysis of EXPAND. Ther Adv Hematol. 2022 Sep 10;13:20406207221118429. doi: 10.1177/20406207221118429. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2011
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: March 16, 2011
• First Posted (Estimated): March 17, 2011

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Polycythemia; Primary Myelofibrosis
• Other Study ID Numbers: CINC424A2201; 2010-023055-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No