Myelofibrosis
Conditions
Keywords
Myelofibrosis, Primary myelofibrosis, PMF, Post polycythemia myelofibrosis, PPV MF, Post-essential thrombocythemia myelofibrosis, PET-MF, INC424, Ruxolitinib
Brief summary
The primary objective of this study was to collect additional safety of INC424 in patients with Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis, who either received prior treatment with commercially available agents or who have never received treatment.
Interventions
DRUGINC424
All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
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
Main Inclusion Criteria: 1. Patients must not be eligible for another ongoing INC424 clinical trial. 2. Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised International Standard Criteria, irrespective of JAK2 mutation status.. 3. Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen (assessment to occur at the Screening Visit). The prognostic factors, defined by the International Working Group are: * Age \> 65 years; * Presence of constitutional symptoms (weight loss, fever, night sweats); * Marked anemia (Hgb \< 10g/dL)\*; * Leukocytosis (history of white blood cell (WBC) \> 25 x109/L); * Circulating blasts \> 1%. \* A hemoglobin value \< 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin \< 10 g/dL for the purpose of evaluation of risk factors. 4. Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion. 5. Patients must have a peripheral blood blast count of \< 10%. 6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 7. Fedratinib pretreated patients with documented complete physical examination including full neurologic examination and cardiology assessment, thiamine level testing, and MRI of the brain if indicated based on signs or symptoms. Patients pretreated with fedratinib should have completed or be receiving thiamine supplementation according to the investigator's instructions. Main
Exclusion criteria
1. Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available). 2. Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ. 3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 4. Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol. 5. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal atrial fibrillation or recent (approximately 6 months) myocardial infarction or acute coronary syndrome. 6. Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 7. Patients with known active hepatitis A, B, C or who are HIV-positive. 8. Patients with inadequate bone marrow reserve at the Baseline visit as demonstrated by: * Absolute neutrophil count (ANC) ≤ 1000/µL. * Platelet count \< 50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions. 9. Patients with any history of platelet counts \< 50,000/µL or ANC \< 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason. 10. In the case of ruxolitinib pretreated patients, ruxolitinib primary resistant patients defined as: • No spleen reduction within the first 12 weeks after front line therapy with ruxolitinib. AND • No reduction in symptoms within the first 12 weeks after first-line treatment with ruxolitinib. 11. In the case of ruxolitinib pretreated patients, patients discontinuing ruxolitinib due to a Grade 4 Adverse event (AE) related or suspected to be related to ruxolitinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years | Baseline up to approximately 5 years | An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Baseline up to approximately 5 years | Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length. Participants with spleen length at baseline more than 10 cm were reported as Responders with spleen reduction of 50% from baseline; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 50% from baseline in spleen length. |
| Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline up to approximately 5 years | ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death. |
| Percentage of Participants With at Least 50% Reduction in Spleen Length | Baseline up to approximately 5 years | Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit). |
| Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status | Baseline up to approximately 5 years | Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cutoff=5.4, range 0-60, FACIT-Fatigue =5 and range=0-52.The median time to first improvement was estimated using the Kaplan Meier method and time to improvement event was determined based on upper bound of the MID. The time to improvement was calculated from the date of first study drug administration. |
| Medical Resource Utilization up to 5 Years | Baseline up to approximately 5 years. | Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years. |
| Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | Baseline and Week 48 | The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of better HRQoL. |
Countries
Algeria, Argentina, Austria, Belgium, Brazil, Canada, Colombia, Czechia, Germany, Greece, Hungary, Ireland, Israel, Italy, Mexico, Morocco, Poland, Portugal, Russia, Saudi Arabia, Slovakia, South Africa, Spain, Thailand, Tunisia
Participant flow
Recruitment details
This was an expanded access study intended to provide an access path to ruxolitinib for patients with Myelofibrosis (MF) and to allow for collection of additional safety and efficacy data for ruxolitinib.
Participants by arm
| Arm | Count |
|---|---|
| INC424 5 - 25 mg twice a day (BID)
INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally. | 2,233 |
| Total | 2,233 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 25 |
| Overall Study | Adverse Event | 405 |
| Overall Study | Death | 101 |
| Overall Study | Disease progression | 204 |
| Overall Study | Lost to Follow-up | 16 |
| Overall Study | Physician Decision | 93 |
| Overall Study | Protocol deviation | 27 |
| Overall Study | Withdrawal by Subject | 79 |
Baseline characteristics
| Characteristic | INC424 |
|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 10.5 |
| ECOG score 0 | 1061 Participants |
| ECOG score 1 | 960 Participants |
| ECOG score 2 | 197 Participants |
| ECOG score 3 | 1 Participants |
| ECOG score 4 | 0 Participants |
| ECOG score Missing | 14 Participants |
| Race/Ethnicity, Customized Chinese | 1 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 509 Participants |
| Race/Ethnicity, Customized Indian (Indian subcontinent) | 1 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants |
| Race/Ethnicity, Customized Mixed Ethnicity | 15 Participants |
| Race/Ethnicity, Customized Others | 1707 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 96 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2087 Participants |
| Sex: Female, Male Female | 1016 Participants |
| Sex: Female, Male Male | 1217 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 205 / 2,233 |
| other Total, other adverse events | 2,008 / 2,233 |
| serious Total, serious adverse events | 830 / 2,233 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above.
Time frame: Baseline up to approximately 5 years
Population: Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| INC424 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years | Adverse Events | 2153 Participants |
| INC424 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years | Serious adverse events | 830 Participants |
Secondary
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years
ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.
Time frame: Baseline up to approximately 5 years
Population: Full analysis set includes all patients who received at least one administration of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Grade 1 | 629 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Grade 0 | 598 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Grade 1 | 377 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Grade 2 | 62 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Grade 3 | 12 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Grade 4 | 7 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Grade 5 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 0 | Worst value post-baseline: Missing | 5 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Grade 0 | 89 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Grade 2 | 187 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Grade 3 | 26 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Grade 4 | 12 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Grade 5 | 1 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 1 | Worst value post-baseline: Missing | 16 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Grade 0 | 3 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Grade 1 | 43 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Grade 2 | 111 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Grade 3 | 20 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Grade 4 | 12 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Grade 5 | 1 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 2 | Worst value post-baseline: Missing | 7 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Grade 0 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Grade 1 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Grade 2 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Grade 3 | 1 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Grade 4 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Grade 5 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 3 | Worst value post-baseline: Missing | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Grade 0 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Grade 1 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Grade 2 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Grade 3 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Grade 4 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Grade 5 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Grade 4 | Worst value post-baseline: Missing | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Grade 0 | 1 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Grade 1 | 8 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Grade 2 | 4 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Grade 3 | 1 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Grade 4 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Grade 5 | 0 Participants |
| INC424 | Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years | Baseline - Missing | Worst value post-baseline: Missing | 0 Participants |
Secondary
Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48
The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of better HRQoL.
Time frame: Baseline and Week 48
Population: Full analysis set includes all patients who received at least one administration of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-Lymphoma Baseline | 42.3 scores on a scale | Standard Deviation 10.2 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-Lymphoma Week 48 | 47.9 scores on a scale | Standard Deviation 8.47 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-Lymphoma TOI Baseline | 77.9 scores on a scale | Standard Deviation 18.99 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-Lymphoma TOI Week 48 | 86.8 scores on a scale | Standard Deviation 16.42 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-Lymphoma total score Baseline | 113.9 scores on a scale | Standard Deviation 24.01 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-Lymphoma total score Week 48 | 123.3 scores on a scale | Standard Deviation 22.34 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-G Baseline | 71.6 scores on a scale | Standard Deviation 15.98 |
| INC424 | Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 | FACT-G Week 48 | 75.5 scores on a scale | Standard Deviation 15.59 |
Secondary
Medical Resource Utilization up to 5 Years
Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years.
Time frame: Baseline up to approximately 5 years.
Population: Full analysis set includes all patients who received at least one administration of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| INC424 | Medical Resource Utilization up to 5 Years | Baseline- Dependency | End of Study - Dependency | 129 Participants |
| INC424 | Medical Resource Utilization up to 5 Years | Baseline- Dependency | End of Study - Independency | 29 Participants |
| INC424 | Medical Resource Utilization up to 5 Years | Baseline- Independency | End of Study - Dependency | 480 Participants |
| INC424 | Medical Resource Utilization up to 5 Years | Baseline- Independency | End of Study - Independency | 1595 Participants |
Secondary
Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length
Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length. Participants with spleen length at baseline more than 10 cm were reported as Responders with spleen reduction of 50% from baseline; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 50% from baseline in spleen length.
Time frame: Baseline up to approximately 5 years
Population: Full analysis set includes all patients who received at least one administration of study drug and were observed from baseline in to the study follow-up period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| INC424 | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-More than 10 cm | 742 Participants |
| INC424 | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Less than 5 cm | NA Participants |
| INC424 | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Between 5 and 10 cm | 421 Participants |
| INC424 - Stable Disease | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Between 5 and 10 cm | 334 Participants |
| INC424 - Stable Disease | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Less than 5 cm | NA Participants |
| INC424 - Stable Disease | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-More than 10 cm | 463 Participants |
| INC424 - Progressive Disease | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Between 5 and 10 cm | 1 Participants |
| INC424 - Progressive Disease | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Less than 5 cm | NA Participants |
| INC424 - Progressive Disease | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-More than 10 cm | 0 Participants |
| INC424 - Missing | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Less than 5 cm | NA Participants |
| INC424 - Missing | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-More than 10 cm | 19 Participants |
| INC424 - Missing | Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length | Spleen length at baseline-Between 5 and 10 cm | 9 Participants |
Secondary
Percentage of Participants With at Least 50% Reduction in Spleen Length
Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit).
Time frame: Baseline up to approximately 5 years
Population: Full analysis set includes all patients who received at least one administration of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INC424 | Percentage of Participants With at Least 50% Reduction in Spleen Length | 71.7 percentage of participants |
Secondary
Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status
Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cutoff=5.4, range 0-60, FACIT-Fatigue =5 and range=0-52.The median time to first improvement was estimated using the Kaplan Meier method and time to improvement event was determined based on upper bound of the MID. The time to improvement was calculated from the date of first study drug administration.
Time frame: Baseline up to approximately 5 years
Population: Full analysis set includes all patients who received at least one administration of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INC424 | Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status | FACT-Lym Total score median time to improvement | 10.9 weeks |
| INC424 | Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status | FACIT - Fatigue score median time to improvement | 4.6 weeks |
| INC424 | Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status | ECOG score median time to improvement | 63.1 weeks |