Open Label Ruxolitinib (INCB018424) in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis

NCT00509899 | Completed Phase 1 Results

• 1 other identifier: INCB 18424-251
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 2

Brief Summary

To determine the safety, tolerability and effectiveness of ruxolitinib (INCB018424), administered orally to patients with Primary Myelofibrosis (PMF), Post Polycythemia Vera Myelofibrosis (PPV-MF) and Essential Thrombocythemia Myelofibrosis (PET-MF).

Conditions

Myelofibrosis; Polycythemia Vera; Thrombocytosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  Treatment-Emergent AEs are events occurring after first drug administration or worsened from baseline. Treatment-Related AEs are those with a definite, probable, possible or missing causality. A serious AE is a medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a medical event requiring intervention to prevent 1 of the above. A severe or life-threatening AE is based on intensity, according to National Cancer Institute-Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) v3.0.

  From Baseline to the interim clinical cut-off date (31 December 2009). The median time on study was 14.8 months, with a range of 26 days to 29.7 months. As of March 1, 2011 the total exposure to ruxolitinib was 269 patient-years.

• Percentage of Participants With Clinical Improvement (CI) Over Time

  Clinical improvement was defined according to the International Working Group Myelofibrosis Research and Treatment criteria, and required 1 of the following: 1. A ≥ 2 g/dL increase in Hemoglobin level or becoming transfusion independent; 2. Either a ≥ 50% reduction in palpable splenomegaly if spleen was ≥ 10 cm at Baseline or a spleen palpable at \> 5 cm at Baseline becomes not palpable; 3. A ≥ 100% increase in platelet count and an absolute platelet count of ≥ 50,000 x 10\^9/L or 4. A ≥ 100% increase in absolute neutrophil count (ANC) and an ANC of ≥ 0.5 x 10\^9/L.

  Week 12, 24, 36, 48 and 60

Secondary Outcomes (6)

• Percentage of Participants Achieving ≥ 50% Reduction From Baseline in Spleen Palpation Length Over Time

  Baseline and Weeks 4, 8, 12, 24, 36, 48 and 60

• Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume Over Time

  Baseline, Weeks 4, 12, 24 and 48

• Change From Baseline in Myelofibrosis Total Symptom Score at Week 24

  Baseline and Week 24

• Change From Baseline to Week 24 in Health-Related Quality of Life

  Baseline and Week 24

• Change From Baseline in Body Weight Over Time

  Baseline and Weeks 4, 8, 12, 24, 36, 48 and 60.

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

All participants received oral ruxolitinib. Patients began treatment with either 10 mg twice a day (bid), 15 mg bid, 25 mg bid, 50 mg bid, 25 mg once a day (qd), 50 mg qd, 100 mg qd, or 200 mg qd, depending on the time period when they entered the study. The doses were titrated based on efficacy and safety to a maximum of 25 mg bid for patients who entered the study after sufficient dosing information had been obtained to define the maximum dose for patients in the study. Patients could continue receiving treatment indefinitely if receiving benefit at a dose that continues to maintain benefit but does not exceed a maximum dose of 25 mg BID.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

5 and 25 mg tablets with a daily dosing range from 10 to 200 mg qd or bid.

Also known as: INCB018424, Jakafi(TM)

Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• Diagnosed with PMF or Post-PV/ET MF
• Patients with myelofibrosis requiring therapy
• Adequate bone marrow reserve

You may not qualify if:

• Received anti-cancer medications or investigational therapy in the past 14 days

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (2)

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Related Publications (3)

• Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010 Sep 16;363(12):1117-27. doi: 10.1056/NEJMoa1002028.

  PMID: 20843246 RESULT

• Verstovsek S, Kantarjian HM, Estrov Z, Cortes JE, Thomas DA, Kadia T, Pierce S, Jabbour E, Borthakur G, Rumi E, Pungolino E, Morra E, Caramazza D, Cazzola M, Passamonti F. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood. 2012 Aug 9;120(6):1202-9. doi: 10.1182/blood-2012-02-414631. Epub 2012 Jun 20.

  PMID: 22718840 RESULT

• Kvasnicka HM, Thiele J, Bueso-Ramos CE, Sun W, Cortes J, Kantarjian HM, Verstovsek S. Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis. J Hematol Oncol. 2018 Mar 15;11(1):42. doi: 10.1186/s13045-018-0585-5.

  PMID: 29544547 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera; Thrombocytosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Platelet Disorders

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

1-855-463-3463

Study Officials

• Srdan Verstovsek, MD, PhD

  M.D. Anderson Cancer Center, Houston, TX

  PRINCIPAL INVESTIGATOR

• Ayalew Tefferi, MD

  Mayo Clinic, Rochester, MN

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: August 1, 2007
• Study Start: June 1, 2007
• Primary Completion: December 1, 2007
• Study Completion: February 1, 2017
• Last Updated: March 12, 2018
• Results First Posted: August 2, 2012

Record last verified: 2018-02

Locations

US (2)