Back to resultsStudy of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients
Primary Purpose
Myelofibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring myelofibrosis, myeloproliferative neoplasms, PMF, PET-MF, PPV-MF
Eligibility Criteria
Inclusion Criteria:
- Participants 18 years of age or older.
- Participants must be diagnosed with primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (PPV-MF), or post-polycythemia vera myelofibrosis (PET-MF).
- Participants with myelofibrosis requiring therapy must be classified as high risk (3 or more prognostic factors), intermediate risk level 2 (2 prognostic factors), or intermediate risk level 1 (1 prognostic factor)defined by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT).
- Participants must have a palpable spleen measuring 5 cm or greater below the costal margin.
Exclusion Criteria:
- Participants with a life expectancy of less than 6 months.
- Participants of childbearing potential who are unwilling to take appropriate precautions to avoid pregnancy or fathering a child.
- Participants with inadequate bone marrow reserve.
- Participants with history of platelet counts < 50,000/μL, platelet transfusion(s), or an absolute neutrophil count < 500/μL in the month prior to Screening.
- Participants with inadequate liver or renal function at Screening and Baseline visits.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ruxolitinib 25 mg SR/10, 15, or 20 mg IR
Arm Description
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With at Least 1 Adverse Event From Baseline Through 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.
Secondary Outcome Measures
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.
Change From Baseline in Spleen Length at Week 16
Spleen length was measured in centimeters by palpation.
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.
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.
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.
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 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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01340651
Brief Title
Study of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis
Keywords
myelofibrosis, myeloproliferative neoplasms, PMF, PET-MF, PPV-MF
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib 25 mg SR/10, 15, or 20 mg IR
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INCB018424
Intervention Description
Ruxolitinib was supplied as SR and IR formulated tablets.
Primary Outcome Measure Information:
Title
Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16
Time Frame
Baseline to Week 16
Title
Overall Response (OR) at Week 16
Description
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
Secondary Outcome Measure Information:
Title
Change From Baseline in Spleen Volume at Week 16
Description
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
Title
Change From Baseline in Spleen Length at Week 16
Description
Spleen length was measured in centimeters by palpation.
Time Frame
Baseline to Week 16
Title
Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 16 From Baseline
Description
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
Title
Change From Baseline in the Total Symptom Score at Week 16
Description
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
Title
Percentage of Participants With a ≥ 50% Reduction From Baseline in the Total Symptom Score at Week 16
Description
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
Title
Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib 25 mg SR on Day 1
Description
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
Title
Time to Reach the Maximum Plasma Concentration (Tmax) of Ruxolitinib 25 mg SR on Day 1
Description
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
Title
Area Under the Plasma Concentration-time Curve (AUC) of Ruxolitinib 25 mg SR on Day 1
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants 18 years of age or older.
Participants must be diagnosed with primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (PPV-MF), or post-polycythemia vera myelofibrosis (PET-MF).
Participants with myelofibrosis requiring therapy must be classified as high risk (3 or more prognostic factors), intermediate risk level 2 (2 prognostic factors), or intermediate risk level 1 (1 prognostic factor)defined by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT).
Participants must have a palpable spleen measuring 5 cm or greater below the costal margin.
Exclusion Criteria:
Participants with a life expectancy of less than 6 months.
Participants of childbearing potential who are unwilling to take appropriate precautions to avoid pregnancy or fathering a child.
Participants with inadequate bone marrow reserve.
Participants with history of platelet counts < 50,000/μL, platelet transfusion(s), or an absolute neutrophil count < 500/μL in the month prior to Screening.
Participants with inadequate liver or renal function at Screening and Baseline visits.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Srdan Verstovsek, MD, PhD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
City
Scottsdale
State/Province
Arizona
Country
United States
City
Winter Park
State/Province
Florida
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
TX
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients
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