The purpose of this study is to determine the safety and tolerability of ruxolitinib (INCB018424) sustained release (SR) formulation in participants with primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF), and post-essential thrombocythemia MF (PET-MF).
The study will enroll approximately 40 participants with PMF, PPV-MF or PET-MF. Participants will take ruxolitinib SR once daily for 16 consecutive weeks and then transition to a comparable twice daily dose regimen of ruxolitinib using the immediate release (IR) tablets which have been under investigation in controlled Phase 1, 2, and 3 clinical trials. Participants receiving benefit from treatment with ruxolitinib may continue further participation with IR tablets up to the time when the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier. Follow-up will occur at least 30 days following the last dose of ruxolitinib.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Ruxolitinib was supplied as SR and IR formulated tablets.
Unnamed facility
Scottsdale, Arizona, United States
Unnamed facility
Winter Park, Florida, United States
Unnamed facility
Houston, Texas, United States
Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16
Time frame: Baseline to Week 16
Overall Response (OR) at Week 16
The investigator graded OR according to the International Working Group for Myelofibrosis Research and Therapy criteria for treatment response. As bone marrow biopsies were not taken after baseline, the best achievable response was clinical improvement which required 1 of the following in the absence of progressive disease (PD): (1) A ≥ 2 g/dL increase in hemoglobin level or (2) either a palpable ≥ 50% reduction of splenomegaly of a spleen ≥ 10 cm at baseline or a spleen palpable at \> 5 cm at baseline becoming not palpable. PD required 1 of the following: (1) Progressive splenomegaly defined by the appearance of previously absent splenomegaly that was palpable at \> 5 cm below the left costal margin or a ≥ 100% increase in palpable distance for baseline splenomegaly of 5-10 cm or a ≥ 50% increase in palpable distance for baseline splenomegaly of \> 10 cm or (2) an increase in peripheral blood blast percentage to ≥ 20% that lasted for ≥ 8 weeks. Stable disease: None of the above.
Time frame: Baseline to Week 16
Change From Baseline in Spleen Volume at Week 16
Spleen volume was measured by magnetic resonance imaging (or by computed tomography \[CT\] in applicable participants). Scans were read by a central reader. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares.
Time frame: Baseline to Week 16
Change From Baseline in Spleen Length at Week 16
Spleen length was measured in centimeters by palpation.
Time frame: Baseline to Week 16
Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 16 From Baseline
Spleen volume was measured by magnetic resonance imaging (or by computed tomography \[CT\] in applicable participants). Scans were read by a central reader. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares.
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Time frame: Baseline to Week 16
Change From Baseline in the Total Symptom Score at Week 16
Symptoms of myelofibrosis were assessed using the modified Myelofibrosis Symptom Assessment Form v2.0 diary that was to be completed by participants each night. The 7 symptoms (night sweats, itchiness, abdominal pain, pain under the ribs on left side, feeling of fullness \[early satiety\], bone/muscle pain, inactivity) were each rated on a scale from 0 (absent) to 10 (worst imaginable). The total symptom score was the sum of 6 of the 7 symptoms (inactivity was not included) and ranged from 0 to 60. A lower score indicated fewer symptoms. A negative change score indicated improvement.
Time frame: Baseline to Week 16
Percentage of Participants With a ≥ 50% Reduction From Baseline in the Total Symptom Score at Week 16
Symptoms of myelofibrosis were assessed using the modified Myelofibrosis Symptom Assessment Form v2.0 diary that was to be completed by participants each night. The 7 symptoms (night sweats, itchiness, abdominal pain, pain under the ribs on left side, feeling of fullness \[early satiety\], bone/muscle pain, inactivity) were each rated on a scale from 0 (absent) to 10 (worst imaginable). The total symptom score was the sum of 6 of the 7 symptoms (inactivity was not included) and ranged from 0 to 60. A lower score indicated fewer symptoms.
Time frame: Baseline to Week 16
Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib 25 mg SR on Day 1
Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. Standard non-compartmental pharmacokinetic methods were used to analyze the ruxolitinib plasma concentration data using WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA). Cmax was taken directly from the observed plasma concentration data.
Time frame: Day 1
Time to Reach the Maximum Plasma Concentration (Tmax) of Ruxolitinib 25 mg SR on Day 1
Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. Standard noncompartmental pharmacokinetic methods were used to analyze the ruxolitinib plasma concentration data using WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA). Tmax was taken directly from the observed plasma concentration data.
Time frame: Day 1
Area Under the Plasma Concentration-time Curve (AUC) of Ruxolitinib 25 mg SR on Day 1
Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. The area under the plasma concentration-time curve (AUC) was derived from the plasma concentrations using a non-compartmental method and computed using the linear trapezoidal rule for increasing concentrations and the log-trapezoidal rule for decreasing concentrations with the software WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA).
Time frame: Day 1