Back to resultsRuxolitinib (INCB018424) in Participants With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia-myelofibrosis and Post Polycythemia Vera-myelofibrosis (PPV-MF)
Primary Purpose
MPN (Myeloproliferative Neoplasms)
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 MPN (Myeloproliferative Neoplasms) focused on measuring PMF, PPV-MF, PET-MF
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy
- Discontinuation of all drugs used to treat underlying MF disease at least 14 days prior to baseline visit
- INR <= 1.5 or PTT value < 1.5 x upper limit of normal (ULN) at study entry
- Hemoglobin level at least 6.5 g/dL at Screening visit
- Willingness to be transfused to treat low hemoglobin levels
Exclusion Criteria:
- Females who are pregnant, unable to comply with birth control use to avoid becoming pregnant or breastfeeding
- Males who cannot comply with birth control use to avoid fathering a child
- Platelet count < 50 x10^9/L or absolute neutrophil count (ANC) < 1 x10^9/L at the Screening visit
- Inadequate liver or renal function; Intracranial bleeds or invasive malignancy over the previous 2 years - international normalized ratio (INR) laboratory values cannot be > 1.5 x upper limit of normal at study entry.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ruxolitinib 5 mg
Arm Description
Participants began administration with 5 mg ruxolitinib twice daily (BID) orally. Beginning at the Week 4 visit, doses of ruxolitinib could be increased in 5 mg once a day (QD) increments every 4 weeks every 4 weeks not to exceed a dose of 25 mg BID.
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose
Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug.
Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03)
Participants with platelet count between 50 and 100 × 10^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count < 25 × 10^9/L.
Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03
Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms.
Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Secondary Outcome Measures
Percent Change in Spleen Volume at Week 24 Compared to Baseline
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant was not a candidate for MRI, or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms..
Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Change in Spleen Length Measured by Palpation
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Percent Change From Baseline in Spleen Length Measured by Palpation
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Patient Global Impression of Change (PGIC) Score at Each Visit
Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, patients rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you've received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01348490
Brief Title
Ruxolitinib (INCB018424) in Participants With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia-myelofibrosis and Post Polycythemia Vera-myelofibrosis (PPV-MF)
Official Title
An Open-Label Assessment of Safety and Efficacy of Ruxolitinib (INCB018424) in Subjects With Primary Myelofibrosis, Post- Essential Thrombocythemia Myelofibrosis, and Post-Polycythemia Vera Myelofibrosis Who Have Platelet Counts of 50 × 10^9/L to 100 × 10^9/L
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
June 15, 2011 (Actual)
Primary Completion Date
December 19, 2018 (Actual)
Study Completion Date
December 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the effects of treatment with ruxolitinib (INCB018424) on spleen volume, symptoms and potential side effects in participants with PMF, PPV-MF and PET-MF who have platelet counts of 50 x 10^9/L to 100 x 10^9/L. It is anticipated that individualized dose optimization from the starting ruxolitinib level of 5 mg bid will be associated with reductions in splenomegaly, MF-associated symptoms and inflammatory cytokine levels.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MPN (Myeloproliferative Neoplasms)
Keywords
PMF, PPV-MF, PET-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
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib 5 mg
Arm Type
Experimental
Arm Description
Participants began administration with 5 mg ruxolitinib twice daily (BID) orally. Beginning at the Week 4 visit, doses of ruxolitinib could be increased in 5 mg once a day (QD) increments every 4 weeks every 4 weeks not to exceed a dose of 25 mg BID.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INCB018424
Intervention Description
Ruxolitinib (INCB018424), 5 mg bid
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose
Description
Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time Frame
Baseline and Week 24
Title
Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose
Description
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
Description
TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug.
Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Time Frame
Up to Week 156
Title
Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03)
Description
Participants with platelet count between 50 and 100 × 10^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count < 25 × 10^9/L.
Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Time Frame
Up to Week 156
Title
Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03
Description
Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms.
Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Time Frame
Up to Week 156
Secondary Outcome Measure Information:
Title
Percent Change in Spleen Volume at Week 24 Compared to Baseline
Description
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant was not a candidate for MRI, or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time Frame
Baseline and Week 24
Title
Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
Description
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms..
Time Frame
Baseline and Week 24
Title
Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline
Description
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline
Description
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
Description
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Time Frame
Baseline and Week 24
Title
Change in Spleen Length Measured by Palpation
Description
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Time Frame
Up to Week 156
Title
Percent Change From Baseline in Spleen Length Measured by Palpation
Description
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. The edge of the spleen was determined by palpation, and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Time Frame
Up to Week 156
Title
Patient Global Impression of Change (PGIC) Score at Each Visit
Description
Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, patients rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you've received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms.
Time Frame
Up to Week 156
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy
Discontinuation of all drugs used to treat underlying MF disease at least 14 days prior to baseline visit
INR <= 1.5 or PTT value < 1.5 x upper limit of normal (ULN) at study entry
Hemoglobin level at least 6.5 g/dL at Screening visit
Willingness to be transfused to treat low hemoglobin levels
Exclusion Criteria:
Females who are pregnant, unable to comply with birth control use to avoid becoming pregnant or breastfeeding
Males who cannot comply with birth control use to avoid fathering a child
Platelet count < 50 x10^9/L or absolute neutrophil count (ANC) < 1 x10^9/L at the Screening visit
Inadequate liver or renal function; Intracranial bleeds or invasive malignancy over the previous 2 years - international normalized ratio (INR) laboratory values cannot be > 1.5 x upper limit of normal at study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Langmuir, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Burbank
State/Province
California
Country
United States
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La Jolla
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California
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United States
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Los Angeles
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California
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United States
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Pomona
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California
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United States
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San Diego
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California
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United States
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New Haven
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Connecticut
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United States
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Fort Myers
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Florida
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United States
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Jacksonville
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Florida
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United States
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Orange City
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Florida
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United States
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Atlanta
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Georgia
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United States
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Augusta
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Georgia
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Chicago
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Illinois
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United States
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Iowa City
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Iowa
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Louisville
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Kentucky
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United States
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New Orleans
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Louisiana
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United States
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Baltimore
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Maryland
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Ann Arbor
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Michigan
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United States
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Southfield
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Michigan
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Saint Louis
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Missouri
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Hackensack
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New Jersey
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Morristown
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New Jersey
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United States
City
Somerville
State/Province
New Jersey
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United States
City
New York
State/Province
New York
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United States
City
Durham
State/Province
North Carolina
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United States
City
Hickory
State/Province
North Carolina
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United States
City
Canton
State/Province
Ohio
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United States
City
Cleveland
State/Province
Ohio
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United States
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Portland
State/Province
Oregon
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Danville
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Pennsylvania
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United States
City
Hershey
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Pennsylvania
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Charleston
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South Carolina
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United States
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Nashville
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Tennessee
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United States
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Houston
State/Province
Texas
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United States
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San Antonio
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Burlington
State/Province
Vermont
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34911667
Citation
Talpaz M, Prchal J, Afrin L, Arcasoy M, Hamburg S, Clark J, Kornacki D, Colucci P, Verstovsek S. Safety and Efficacy of Ruxolitinib in Patients with Myelofibrosis and Low Platelet Counts (50 - 100 x 109/L): Final Analysis of an Open-Label Phase 2 Study. Clin Lymphoma Myeloma Leuk. 2022 May;22(5):336-346. doi: 10.1016/j.clml.2021.10.016. Epub 2021 Nov 2.
Results Reference
derived
PubMed Identifier
24283202
Citation
Talpaz M, Paquette R, Afrin L, Hamburg SI, Prchal JT, Jamieson K, Terebelo HR, Ortega GL, Lyons RM, Tiu RV, Winton EF, Natrajan K, Odenike O, Claxton D, Peng W, O'Neill P, Erickson-Viitanen S, Leopold L, Sandor V, Levy RS, Kantarjian HM, Verstovsek S. Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. J Hematol Oncol. 2013 Oct 29;6(1):81. doi: 10.1186/1756-8722-6-81.
Results Reference
derived
Learn more about this trial
Ruxolitinib (INCB018424) in Participants With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia-myelofibrosis and Post Polycythemia Vera-myelofibrosis (PPV-MF)
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