Clinical trial NCT02087059: A Clinical Study of Ruxolitinib in Patients With Primary Myelofibrosis (PM), Post-polycythemia Vera (PV) Myelofibrosis, or Post-essential Thrombocythemia (ET) Myelofibrosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Myelofibrosis (MF)
Keywords: Post-Polycythemia Vera (PV) MF
Post-Essential Thrombocythemia (ET) MF
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-03-14
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 24 weeks
Secondary outcomes:
measure: Charge in Spleen Size From Baseline at Specified Week
timeFrame: Baseline, 24 weeks
measure: Charge in Spleen Size From Baseline up to the Specified Week
timeFrame: Baseline, 24 weeks
measure: Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time
timeFrame: 24 weeks
measure: Summary of Summary of EORTC QLQ-C30 Responses by Time
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Matsuyama
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Toon-city
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kurume-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Maebashi-city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kobe-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kobe-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Kyoto-city
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Tsu-city
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Sendai-city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Miyazaki-city
country: Japan
facility: Novartis Investigative Site
state: Miyazaki
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Hirakata-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: OsakaSayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Shimotsuke-city
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-city
country: Japan
facility: Novartis Investigative Site
state: Yamanashi
city: Akita
country: Japan
facility: Novartis Investigative Site
city: Gifu
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: