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

Phase 3

Completed

• Conditions: Primary Myelofibrosis (MF)
• Interventions: Drug: Ruxolitinib

• Registration Number: NCT02087059
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-03-12
• Study First Submitted QC: 2014-03-12
• Study First Posted: 2014-03-14
• Study Start: 2014-04
• Primary Completion: 2015-03
• Study Completion: 2015-04
• Results First Submitted: 2016-04-11
• Status Verified: 2016-05
• Results First Submitted QC: 2016-05-26
• Last Update Submitted: 2016-05-26
• Results First Posted: 2016-07-11
• Last Update Posted: 2016-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ruxolitinib	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	24 weeks

Secondary Outcome Measures

Name	Time	Method
Charge in Spleen Size From Baseline at Specified Week	Baseline, 24 weeks	Number of patients with spleen length reduced by ≥ 50% at specified week
Charge in Spleen Size From Baseline up to the Specified Week	Baseline, 24 weeks	Number of patients with spleen length reduced by ≥ 50% up to specified week
Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time	24 weeks	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
Summary of Summary of EORTC QLQ-C30 Responses by Time	24 weeks	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇯🇵 Gifu, Japan