Blood and Lymph Conditions

All Conditions

Neoplasms

Rare Diseases

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

Participants began administration with 25 mg ruxolitinib sustained release (SR) once daily (QD). After 8 weeks, if there was inadequate efficacy, the dose level could be titrated to 50 mg SR QD or 25 mg SR every other day (QOD) alternating with 50 mg SR QOD. At Week 16, participants transitioned to ruxolitinib 10, 15, or 20 mg immediate release (IR) orally twice daily. Participants who continued to demonstrate benefit in the opinion of the investigator could remain on ruxolitinib IR until the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier; the dose received was based on platelet counts at the time of transition.

Ruxolitinib was supplied as SR and IR formulated tablets.

Ruxolitinib

Srdan Verstovsek, MD, PhD

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 of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients

An Open-label Assessment of Once-daily Dosing of a Sustained Release (SR) Formulation of INCB018424 in Patients With Primary Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, and Post-polycythemia Vera Myelofibrosis

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.

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.

Spleen length was measured in centimeters by palpation.

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.

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.

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.

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.

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).

Incyte Corporation

Safety population: All enrolled participants who took at least 1 dose of study drug.

Participants began administration with 25 mg ruxolitinib sustained release (SR) once daily (QD). After 8 weeks, if there was inadequate efficacy, the dose level could be titrated to 50 mg SR QD or 25 mg SR every other day (QOD) alternating with 50 mg SR QOD.

Ruxolitinib - Weeks 1-16

At Week 16, participants transitioned to ruxolitinib 10, 15, or 20 mg immediate release (IR) orally twice daily up to when the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier; the dose received was based on platelet counts at the time of transition.

Ruxolitinib - After Week 16

Age, Continuous

Sex: Female, Male

Intent-to-treat population: All enrolled participants.

Study Director

Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16

Clinical improvement

Stable disease

Progressive disease

Overall Response (OR) at Week 16

Change From Baseline in Spleen Volume at Week 16

Change From Baseline in Spleen Length at Week 16

Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 16 From Baseline

Change From Baseline in the Total Symptom Score at Week 16

Percentage of Participants With a ≥ 50% Reduction From Baseline in the Total Symptom Score at Week 16

Participants began administration with 25 mg ruxolitinib sustained release (SR) once daily (QD).

Pharmacokinetic evaluable participants: All enrolled participants who received at least 1 dose of study medication and provided at least 1 plasma sample.

Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib 25 mg SR on Day 1

Time to Reach the Maximum Plasma Concentration (Tmax) of Ruxolitinib 25 mg SR on Day 1

Area Under the Plasma Concentration-time Curve (AUC) of Ruxolitinib 25 mg SR on Day 1

Participants began administration with 25 mg ruxolitinib sustained release (SR) once daily (QD). After 8 weeks, if there was inadequate efficacy, the dose level could be titrated to 50 mg SR QD or 25 mg SR every other day (QOD) alternating with 50 mg SR QOD. At Week 16, participants transitioned to ruxolitinib 10, 15, or 20 mg immediate release (IR) orally twice daily up to when the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier; the dose received was based on platelet counts at the time of transition.

Spots Global Cancer Trial Database for Study of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients

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Study Description

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