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

Primary Myelofibrosis (MF) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02087059
• Other study ID #: CINC424AJP01
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2014
• Last updated: February 3, 2016
• Start date: April 2014
• Est. completion date: March 2015

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis
• Primary Myelofibrosis (MF)
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Ruxolitinib

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Akita
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chuo-city	Yamanashi
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Gifu
Japan	Novartis Investigative Site	Hirakata-city	Osaka
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Kurume-city	Fukuoka
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Maebashi-city	Gunma
Japan	Novartis Investigative Site	Matsuyama	Ehime
Japan	Novartis Investigative Site	Miyazaki-city	Miyazaki
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	OsakaSayama	Osaka
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Shimotsuke-city	Tochigi
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita-city	Osaka
Japan	Novartis Investigative Site	Toon-city	Ehime
Japan	Novartis Investigative Site	Tsu-city	Mie

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		24 weeks	Yes
Secondary	Charge in spleen size from baseline		Baseline, 24 weeks	No
Secondary	Clinical symptoms will be evaluated using th seven-day modified MFSAF questionnaires		24 weeks	No
Secondary	Quality of Life will be evaluated using the EORTC QLQ-C30		24 weeks	No