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)

NCT01317875 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: CINC424A22012010-023055-29
• Study Type: interventional
• Target: 69
• Locations: 8 countries
• Sites: 18

Brief Summary

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

Conditions

Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of Treatment Emergent Adverse Events (TEAE's)

  approximately 4 years

• Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length

  24 weeks

• Change in Spleen Length as Measure by Palpation Over Time

  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)

  24 weeks

• PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12)

  24 weeks

Study Arms (2)

Stratum -1

EXPERIMENTAL

Participants with baseline Platelet counts of 75-99 x10\^9/L

Drug: Ruxolitinib

Stratum -2

EXPERIMENTAL

Participants with baseline Platelet counts of 50-74 x10\^9/L

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

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

Also known as: INCB018424

Stratum -1; Stratum -2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Incyte Corporation: lead
• Novartis: collaborator

Study Sites (18)

Unknown Facility

Winter Park, Florida, 32789, United States

Location

Unknown Facility

Baltimore, Maryland, 21229, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Vienna, Austria

Location

Unknown Facility

Nanjing, Jiangsu, China

Location

Unknown Facility

Chengdu, Sichuan, China

Location

Unknown Facility

Hangzhou, Zhejiang, China

Location

Unknown Facility

Beijing, China

Location

Unknown Facility

Angers, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Pierre-Bénite, France

Location

Unknown Facility

Leipzig, Germany

Location

Unknown Facility

Florence, Italy

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Terni, Italy

Location

Unknown Facility

Rotterdam, Netherlands

Location

Unknown Facility

Belfast, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36105914 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Incyte Corporation Call Center, Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Mark Jones, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 14, 2011
• First Posted: March 17, 2011
• Study Start: March 31, 2011
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: August 22, 2025
• Results First Posted: March 9, 2022

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); CN (4); GB (2); FR (3); AU (1); NL (1); DE (1); US (3)