Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF

Study Overview
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Brief Summary
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The objective of this study was to determine the efficacy of INC424 as assessed by reduction in spleen volume in patients with primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF. The safety and tolerability of INC424 and the effects of INC424 on patient reported outcomes and the duration of response as assessed by reduction in spleen volume was also assessed.

Official Title
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A Multi-national Open-label Phase II Study of the JAK Inhibitor INC424 in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis

Conditions
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Primary Myelofibrosis (MF), Post-Polycythemia Vera (PV) MF, Post-Essential Thrombocythemia (ET) MF

Intervention / Treatment
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* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Diagnosis of primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF Enlarged spleen, measuring 5 cm or greater from the costal margin Must have two or more of the following risk factors: Over 65 years old Have the following symptoms often associated with MF: loss of weight, fever, night sweats Have a low red blood cell count (anemia - hemoglobin < 10 g/dL) Have a high white blood cell count (history of white blood cell count > 25,000/uL) Have high circulating blasts (> or = 1%) as measured by blood tests Should have circulating blasts <10% (as measured by blood tests) Should be capable of self-care Should have adequate bone marrow reserve Should not have the option of stem cell transplantation Should discontinue any prior or ongoing treatment for myelofibrosis prior to entering the study Had no prior treatment with another JAK inhibitor Exclusion Criteria: Does not have adequate liver or kidney function (as measured by blood tests) Has an active infection (bacterial, viral, etc.) Has active hepatitis A, B, or C or positive for HIV Has another cancer that needs active intervention Had a history of bleeding disorder Had a history of very low platelet counts (as measured by blood tests) not related to treatment of MF Had radiation of the spleen within 1 year of joining the study Does not have adequate heart function Sufficient time has elapsed between stopping previous treatment for MF and joining the study Females who are pregnant or breast-feeding Not able to sign informed consent Has any other active medical conditions that the doctor deems may compromise your safety or ability to join in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm. | Drug: Ruxolitinib<br>* INC424 Tablet for oral use, provided in 5 mg bottles. The dosage strength was 5 mg/tablet INC424 phosphate (free base equivalent).<br>* Other names: INC424;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24 | The primary measure of spleen size was by MRI. MRIs were performed with a body coil because the objective was to measure organ volume only, not to assess for lesions. MRIs were performed by local radiologists who were instructed not to provide a quantitative measure of spleen volume, but could provide a qualitative assessment such as enlarged, smaller, larger, etc. The scans from an individual patient were to be read by a central reader upon transfer from the site radiologist. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Each Scheduled Time Point - Best Response | The best response rate was defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline at any post-baseline assessment. The best response rate was estimated with an associated 95% confidence interval. | Weeks 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, at any time point | 
| Kaplan Meier Estimates of Duration of Response of at Least ≥ 35% Reduction From Baseline in Spleen Volume Per Kaplan Meier Estimates | For patients who had at least one ≥ 35% reduction in spleen volume from baseline at postbaseline, the duration of response was calculated. The start date of the duration was defined as the first spleen volume measurement that was ≥ 35% reduction from baseline, and the end date of the response duration was defined as the earliest of the following: death, A ≥ 25% increase in spleen volume by MRI (or CT in applicable patients) compared to baseline, Splenic irradiation, Leukemic transformation as defined by a bone marrow or a peripheral blood blast count of ≥ 20%, Splenectomy. Duration of response is calculated only for participants who achieved at least one measured >= 35% reduction in spleen volume at any time. | Weeks 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240 | 
| Change in EORTC QLQ-C30 Scores From Baseline in at Week 24 | Patient reported outcomes regarding the impact of MF on patients were assessed using the EORTC QLQ-C30. Data from the EORTC QLQ-C30 questionnaire was analyzed using the standardized scores. There were 2 categories to this scale: Functional/QOL scale and Symptom and Other items scale. For each sub-scale, the raw scores were standardized in order to obtain scores ranging from 0 to 100. For Functional/QOL subscales: a higher score represents a higher/better level of functioning. For Symptoms and Other items subscales: a higher score represents worse level of symptoms. The absolute change from baseline was calculated for each scale and summarized descriptively by scheduled visit. | Baseline, Week 24 | 
| Change in Total Symptom Score From Baseline at Week 24 as Measured by Seven-day Modified MFSAF v2.0 | The Seven-day modified MFSAF v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. Symptoms of myelofibrosis (MF) were assessed using this instrument & included filling up quickly/early satiety, abdominal discomfort, pain under the ribs, night sweats, itching, bone/muscle pain & inactivity. The first 6 items assessed MF symptom severity at its worst as recalled & the seventh captured MF-related inactivity in the 7 days prior to the clinic visit assessment. All 7 items asked subjects to record their answers on an 11-point numeric rating scale (NRS) (0=Absent, 10=Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score, defined as the sum of the 6 individual symptom scores other than the inactivity score (each with 0-10 point scale) collected on the same week. The total symptom scale ranges from 0 -60 where higher score indicates a worse level of the condition. | Baseline, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MF, Primary Myelofibrosis (MF), Post-Polycythemia Vera (PV) MF, Post-Essential Thrombocythemia (ET) MF, post-PV MF, post-ET MF, INC424, Ruxolitinib, Myelofibrosis