Primary Myelofibrosis (MF)
Conditions
Keywords
Post-Polycythemia Vera (PV) MF, Post-Essential Thrombocythemia (ET) MF
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.
Interventions
DRUGRuxolitinib
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Disease Progression | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Ruxolitinib |
|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 49 / 51 |
| serious Total, serious adverse events | 12 / 51 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs, regardless of study treatment relationship | 50 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs suspected to be related to study treatment | 46 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | SAEs, regardless of study treatment relationship | 12 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | SAEs suspected to be related to study treatment | 5 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs of CTC grade 3/4, regardless study treatment | 36 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs of CTC grade 3/4 suspected related treatment | 33 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs leading to the study treatment discontinuation | 5 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs requiring reduction or interruption treatment | 38 Participants |
| Ruxolitinib | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | AEs requiring concomitant medication | 33 Participants |
Secondary
Charge in Spleen Size From Baseline at Specified Week
Number of patients with spleen length reduced by ≥ 50% at specified week
Time frame: Baseline, 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 2 | 12 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 4 | 14 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 8 | 14 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 12 | 11 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 16 | 14 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 20 | 13 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline at Specified Week | Week 24 | 15 particiapants |
Secondary
Charge in Spleen Size From Baseline up to the Specified Week
Number of patients with spleen length reduced by ≥ 50% up to specified week
Time frame: Baseline, 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Charge in Spleen Size From Baseline up to the Specified Week | Week 4 | 18 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline up to the Specified Week | Week 8 | 22 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline up to the Specified Week | Week 12 | 23 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline up to the Specified Week | Week 16 | 26 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline up to the Specified Week | Week 20 | 26 particiapants |
| Ruxolitinib | Charge in Spleen Size From Baseline up to the Specified Week | Week 24 | 26 particiapants |
Secondary
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.
Time frame: 24 weeks
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Cognitive Functioning week 24 (n=43) | 79.84 units on a scale | Standard Deviation 17.653 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Physical Functioning 24(n=43) | 86.67 units on a scale | Standard Deviation 17.959 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Physical Functioning baseline | 79.35 units on a scale | Standard Deviation 17.951 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Role Functioning Baseline(n=51) | 77.78 units on a scale | Standard Deviation 23.254 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Role Functioning Week 24(n=43) | 83.72 units on a scale | Standard Deviation 19.068 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Emotional Functioning Baseline(n=51) | 85.46 units on a scale | Standard Deviation 17.705 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Emotional Functioning Week 24(n=43) | 92.05 units on a scale | Standard Deviation 13.357 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Cognitive Functioning Baseline(n=51) | 78.43 units on a scale | Standard Deviation 20.356 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Social Functioning Baseline (n=51) | 85.62 units on a scale | Standard Deviation 19.154 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Social Functioning week 24(n=43) | 87.60 units on a scale | Standard Deviation 17.852 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Global Health Status/QOL Baseline (n=51) | 55.72 units on a scale | Standard Deviation 22.882 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Global Health Status/QOL week 24 (n=43) | 66.47 units on a scale | Standard Deviation 22.456 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Fatigue Baseline(n=51) | 40.31 units on a scale | Standard Deviation 23.787 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Fatigue week 24 (n=43) | 28.68 units on a scale | Standard Deviation 23.412 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Nausea and Vomiting baseline (n=51) | 4.90 units on a scale | Standard Deviation 13.862 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Nausea and Vomiting week 24 (n=43) | 0.39 units on a scale | Standard Deviation 2.542 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Pain Baseline | 21.57 units on a scale | Standard Deviation 21.678 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Pain week 24 (n=43) | 10.08 units on a scale | Standard Deviation 15.911 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Dyspnoea baseline (n=51) | 22.88 units on a scale | Standard Deviation 25.377 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Dyspnoea Week 24 (n=43) | 25.58 units on a scale | Standard Deviation 23.946 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Insomnia baseline (n=51) | 23.53 units on a scale | Standard Deviation 29.283 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Insomnia Week 24 (n=43) | 15.50 units on a scale | Standard Deviation 23.4 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Appetite Lose baseline (n=51) | 21.57 units on a scale | Standard Deviation 27.787 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Appetite Lose Week 24 (n=43) | 9.30 units on a scale | Standard Deviation 16.786 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Constipation baseline (n=51) | 8.50 units on a scale | Standard Deviation 20.916 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Constipation Week 24 (n=43) | 8.53 units on a scale | Standard Deviation 16.416 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Diarrhoea baseline (n=51) | 18.30 units on a scale | Standard Deviation 24.325 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Diarrhoea Week 24 (n=43) | 12.40 units on a scale | Standard Deviation 23.029 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Financial Difficulties baseline (n=51) | 15.69 units on a scale | Standard Deviation 25.257 |
| Ruxolitinib | Summary of Summary of EORTC QLQ-C30 Responses by Time | Financial Difficulties Week 24 (n=43) | 20.93 units on a scale | Standard Deviation 30.012 |
Secondary
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
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Pain under ribs on left week 24 (=43) | 0.7 score on a scale | Standard Deviation 1.26 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Feeling of fullness Baseline (n=51) | 3.2 score on a scale | Standard Deviation 2.91 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Total symptom score week 24 (n=43) | 5.7 score on a scale | Standard Deviation 6.48 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Night Sweats baseline (n=51) | 2.9 score on a scale | Standard Deviation 3.07 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Night Sweats week 24 (n=43) | 0.6 score on a scale | Standard Deviation 1.35 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Itching baseline (n=51) | 1.8 score on a scale | Standard Deviation 2.39 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Itching week 24 (n=43 | 0.6 score on a scale | Standard Deviation 1.25 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Abdominal Discomfort baseline( n=51) | 4.4 score on a scale | Standard Deviation 3.18 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Abdominal Discomfort week 24(n=43) | 1.4 score on a scale | Standard Deviation 1.84 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Pain under ribs on left Baseline (=51) | 2.2 score on a scale | Standard Deviation 2.72 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Feeling of fullness week 24 (n=43) | 1.3 score on a scale | Standard Deviation 1.8 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Bone/muscle pain Baseline (n=51) | 2.3 score on a scale | Standard Deviation 2.83 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Bone/muscle pain week 24 (n=43) | 1.0 score on a scale | Standard Deviation 1.83 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Degree of inactivity Baseline (n=51) | 2.3 score on a scale | Standard Deviation 2.84 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Degree of inactivity week 24 (n=43) | 1.0 score on a scale | Standard Deviation 1.66 |
| Ruxolitinib | Summary of Total Symptom Score as Measured by Seven-day Modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 by Time | Total symptom score baseline (n=51) | 16.8 score on a scale | Standard Deviation 12.3 |