A Clinical Study of Ruxolitinib in Patients With Primary Myelofibrosis (PM), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis

A Multicenter, Open-label Clinical Study of the JAK Inhibitor Ruxolitinib (INC424) in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis

This is an open-label, multicenter clinical study in order to collect and examine data concerning the safety and efficacy of ruxolitinib in patients with Primary Myelofibrosis (MF), Post-Polycythemia Vera (PV) MF, Post-Essential Thrombocythemia (ET) MF.

Study Overview

• Status: Completed
• Conditions: Primary Myelofibrosis (MF)
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan, 010-8543
    • Novartis Investigative Site
  • Gifu, Japan, 501-1194
    • Novartis Investigative Site
  • Aichi
    • Nagoya-city, Aichi, Japan, 467-8602
      • Novartis Investigative Site
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Novartis Investigative Site
    • Toon-city, Ehime, Japan, 791-0295
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
    • Kurume-city, Fukuoka, Japan, 830-0011
      • Novartis Investigative Site
  • Gunma
    • Maebashi-city, Gunma, Japan, 371-8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 060-8543
      • Novartis Investigative Site
  • Hyogo
    • Kobe-city, Hyogo, Japan, 650-0017
      • Novartis Investigative Site
    • Kobe-city, Hyogo, Japan, 650-0047
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 606-8507
      • Novartis Investigative Site
  • Mie
    • Tsu-city, Mie, Japan, 514-8507
      • Novartis Investigative Site
  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
      • Novartis Investigative Site
  • Miyazaki
    • Miyazaki-city, Miyazaki, Japan, 889-1692
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • Hirakata-city, Osaka, Japan, 573-1191
      • Novartis Investigative Site
    • OsakaSayama, Osaka, Japan, 589-8511
      • Novartis Investigative Site
    • Suita-city, Osaka, Japan, 565-0871
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuke-city, Tochigi, Japan, 329-0498
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Novartis Investigative Site
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Novartis Investigative Site
  • Yamanashi
    • Chuo-city, Yamanashi, Japan, 409-3898
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥18 years of age
2. Diagnosis of PMF, PPV-MF, or PET-MF, regardless of JAK2 mutational status. The diagnostic of PMF will be according to the World Health Organization (WHO) criteria (Thiele et al., 2008) and PPV-MF and PET-MF according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria (Barosi et al., 2008).
3. At least one risk factors provided in the definition of IWG-MRT (Cervantes et al., 2009; classified as intermediate risk-1, intermediate risk-2, or high risk)
4. Patients with intermediate risk-1 (patients who have only one of the IMG-MRT risk factors indicated above ) must have palpable splenomegaly with a length of ≥5 cm from the costal margin to the point of the greatest spleen protrusion.
5. Proportion of blasts in peripheral blood <10%
6. ECOG performance status of 0 to 2

7. The following values for bone marrow function prior to treatment:

   1. Absolute neutrophil count ≥1,000/μL, and
   2. Platelet count ≥50,000/μL without administration of a growth factor, thrombopoietin, or platelet transfusion
8. Stem cell transplantation is not a treatment option at present because it is not indicated or because there are no suitable donors.
9. All drugs used to treat MF were discontinued at least 28 days before treatment initiation.
10. Informed consent form should be signed before any screening procedures is performed

Exclusion Criteria:

1. Hepatic or renal impairment as indicated by the following:

   • Direct bilirubin ≥2-fold than the upper limit of normal (ULN)
   • Alanine aminotransferase (ALT) >2.5-fold ULN
   • Creatinine >2.0 mg/dL
2. Clinically significant infection by bacteria, fungus, mycobacteria, parasite, or virus (screening and enrollment postponed until completion of antibiotic treatment in patients with an acute bacterial infection that requires antibiotic use)
3. Active hepatitis A, B, or C or HIV infection defined by a positive IgM-HA Ab test [hepatitis A virus antibody (immunoglobulin M [IgM])], HBs Ag test (hepatitis B surface antigen), HCV Ab test (hepatitis C virus antibody), or HIV Ab (human immunodeficiency virus antibody) at screening.
4. History of malignancy within the previous 3 years, except for early-stage squamous cell carcinoma and basal cell carcinoma.
5. History of serious congenital or acquired hemorrhagic disease
6. Previous platelet count <25,000/μL or absolute neutrophil count <500/μL, except for patients currently undergoing treatment for a myeloproliferative neoplasm or cytotoxic therapy for any other reason.
7. Splenic irradiation within 12 months before screening
8. Administration of hematopoietic growth factor receptor agonists (erythropoietin, granulocyte colony stimulating factor, romiplostim, eltrombopag) within 14 days before screening or 28 days before treatment initiation.
9. Currently receiving another investigational drug, or received another investigational drug within 30 days before the start of treatment.
10. History of myocardial infarction or acute coronary syndrome within 6 months before screening
11. Poorly controlled or unstable angina at present
12. Rapid or paroxysmal atrial fibrillation at present
13. Active alcohol or drug addiction that could hinder the patient's ability to comply with the study's requirements
14. Pregnant or currently breastfeeding woman
15. Women of childbearing potential or men with reproductive ability who are unwilling to take appropriate contraception measures
16. Patient with any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
17. History of hypersensitivity to the study drug or a drug with a similar chemical structure

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib; Ruxolitinib was administered orally twice daily at the starting dose of 5 mg, 15 mg or 20 mg bid based on Baseline platelet counts. The dosage was subsequently adjusted for safety and efficacy so that each patient was titrated to their most appropriate dose.	Drug: Ruxolitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Charge in Spleen Size From Baseline at Specified Week	Number of patients with spleen length reduced by ≥ 50% at specified week	Baseline, 24 weeks
Charge in Spleen Size From Baseline up to the Specified Week	Number of patients with spleen length reduced by ≥ 50% up to specified week	Baseline, 24 weeks
Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time	The modified MFSAF v2.0 diary captures a patient's symptom severity on a scale of 0 (absent) to 10 (worst imaginable),with a maximal summary score of 60	24 weeks
Summary of Summary of EORTC QLQ-C30 Responses by Time	The QLQ-C30 version 1.0 (QLQ-C30) incorporates five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhea) and perceived financial impact of the disease.All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	24 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: May 26, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: CINC424AJP01