Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis
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ClinicalTrials.gov Identifier: NCT01445769 |
Recruitment Status
:
Completed
First Posted
: October 4, 2011
Results First Posted
: September 19, 2014
Last Update Posted
: September 19, 2014
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Condition or disease | Intervention/treatment | Phase |
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Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis | Drug: Ruxolitinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 45 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | An Open-label Assessment of an Alternative Dosing Strategy of Ruxolitinib in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, and Post-essential Thrombocythemia Myelofibrosis |
Study Start Date : | September 2011 |
Actual Primary Completion Date : | March 2013 |
Actual Study Completion Date : | April 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: Ruxolitinib
Participants initially received ruxolitinib 10 mg twice a day (bid) for 24 weeks. Dose increases of 5 mg bid were possible at Weeks 12 and 18 up to a maximum dose of 20 mg bid.
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Drug: Ruxolitinib
Ruxolitinib was provided as 5 mg tablets. Dose increases were only permitted at wks 12 & 18 for lack of efficacy. Increases were restricted to patients who didn't meet criteria for a dose hold over the prior 6 wks, had a platelet count ≥ 100 x 10^9/L at wk 12 or ≥ 150 x 10^9/L at wk 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin was reduced by less than 40% relative to Baseline. Dose increases were elective and not required. Subjects were permitted a dose increase of 5 mg BID to 15 mg BID at wk 12 and to a maximum of 20 mg BID at wk 18. The protocol required dose decreases for thrombocytopenia (platelets <100 x 10^9/L) or protocol-defined anemia (decline in hemoglobin of at least 2 g/dL to a level < 8 g/dL, development of transfusion dependence, or a 50% increase in transfusion requirements for transfusion dependent subjects).
Other Names:
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- Mean Percentage Change From Baseline in Spleen Volume at Week 24 [ Time Frame: Baseline to Week 24 ]Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
- Median Percent Change From Baseline in Spleen Volume at Week 24 [ Time Frame: Baseline to Week 24 ]Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
- Mean Percentage Change From Baseline in the Total Symptom Score at Week 24 [ Time Frame: Baseline to Week 24 ]Symptoms of myelofibrosis were assessed using a symptom diary, the modified Myelofibrosis Symptom Assessment Form (MFSAF v2.0). Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. Symptoms assessed included night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), muscle/bone pain, and inactivity. The daily total symptom score (TSS) was the sum of the first 6 individual symptom scores (each on a scale of 0-10). Inactivity was not included in the total score. The Baseline TSS was the mean of daily total symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 60. The Week 24 TSS was the mean of the daily total symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 60. A higher score indicates worse symptoms. A negative change score indicates improvement.
- Median Percent Change From Baseline in the Total Symptom Score at Week 24 [ Time Frame: Baseline to Week 24 ]Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. Symptoms assessed included night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), muscle/bone pain, and inactivity. The daily TSS was the sum of the first 6 individual symptom scores (each on a scale of 0-10). Inactivity was not included in the total score. The Baseline total symptom score was the mean of daily total symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 60. The Week 24 total symptom score was the mean of the daily total symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 60. A higher score indicates worse symptoms. A negative change score indicates improvement.
- Percentage of Participants With a ≥ 35% Reduction From Baseline in Spleen Volume at Week 24 [ Time Frame: Baseline to Week 24 ]Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
- Percentage of Participants With a ≥ 10% Reduction From Baseline in Spleen Volume at Week 24 [ Time Frame: Baseline to Week 24 ]Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
- Percentage of Participants With a ≥ 50% Improvement From Baseline in Total Symptom Score at Week 24 [ Time Frame: Baseline to Week 24 ]Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. Symptoms assessed included night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), muscle/bone pain, and inactivity. The daily total symptom score was the sum of the first 6 individual symptom scores (each on a scale of 0-10). Inactivity was not included in the total score. The Baseline total symptom score was the mean of daily total symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 60. The Week 24 total symptom score was the mean of the daily total symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 60. A higher score indicates worse symptoms. A negative change score indicates improvement.
- Mean Percentage Change From Baseline in Palpable Spleen Length at Week 24 [ Time Frame: Baseline to Week 24 ]Spleen length was assessed by manual palpation. 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.
- Median Percent Change From Baseline in Palpable Spleen Length at Week 24 [ Time Frame: Baseline to Week 24 ]Spleen length was assessed by manual palpation. 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.
- Percentage of Participants With a ≥ 50% Improvement From Baseline in Their Transfusion Status or With New Transfusion Independence Status for Those Participants Who Were Transfusion Dependent at Baseline [ Time Frame: Baseline to Week 24 ]
Transfusion dependence at Baseline is defined as subjects who received ≥ 2 units of red blood cell product(s) in the 12 consecutive weeks prior to the date of first dose.
Transfusion independence On-Study is defined as subjects who received 0 units of red blood cell products over any 12-week period after starting dosing with ruxolitinib.
Improvement in transfusion dependence On-Study is defined as a 50% or greater reduction in the frequency of red blood cell transfusions over any 12-week period after starting dosing with ruxolitinib.
- Percentage of Participants With Clinically Notable Anemia [ Time Frame: Baseline to Weeks 12, 18 and 24 ]Clinically Notable Anemia was a pre-specified safety parameter examined at Weeks 12, 18 and 24 and defined as: 1) New onset Grade 3 or higher anemia in subjects who are transfusion independent at Baseline, 2) New onset transfusion dependence in subjects who are transfusion independent at Baseline, defined as receipt of ≥ 2 units in ≤ a 12-week interval, 3) 50% increase in transfusions compared to Baseline in subjects who are transfusion dependent at Baseline.
- Mean Percentage Change in Abdominal Symptom Scores at Week 24. [ Time Frame: Week 24 ]Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. The abdominal symptom score was the sum of 3 individual symptom scores (abdominal discomfort, pain under ribs on left side, and feeling of fullness [early satiety]), each on a scale of 0 to 10. A higher score indicates worse symptoms. A negative change score indicates improvement. The Baseline abdominal symptom score was the mean of daily abdominal symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 30. The Week 24 abdominal symptom score was the mean of the daily abdominal symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 30.
- Median Percentage Change in Abdominal Symptom Scores at Week 24. [ Time Frame: Week 24 ]Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. The abdominal symptom score was the sum of 3 individual symptom scores (abdominal discomfort, pain under ribs on left side, and feeling of fullness [early satiety]).
- Number of Participants With Grade 3 or Grade 4 Adverse Events [ Time Frame: Baseline to the end of the study ]
- Dose Distribution at Week 24 [ Time Frame: Week 24 ]Average Daily Dose for the last 28 days on study.

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) as confirmed by bone marrow biopsy.
- Must score at least 2 points on the Dynamic International Prognostic Scoring System (DIPSS) scale for prognostic risk factors.
- Peripheral blast count < 5% at both Screening and Baseline hematology assessments.
- Must discontinue all drugs used to treat underlying myelofibrosis (MF) disease no later than Day -1 (the day prior to starting ruxolitinib).
- Must have hemoglobin value ≥ 6.5 g/dL and be willing to receive blood transfusions.
- Platelet count ≥ 100*10^9/L.
- Must have a palpable spleen.
Exclusion Criteria:
- Inadequate liver or bone marrow reserves, end stage renal disease on dialysis, clinically significant concurrent infections requiring therapy, or unstable cardiac function.
- Invasive malignancies over the previous 5 years (except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers).
- Splenic irradiation within 6 months prior to receiving the first dose of study medication.
- Life expectancy less than 6 months.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01445769
United States, California | |
Highland, California, United States | |
La Jolla, California, United States | |
Los Angeles, California, United States | |
United States, Florida | |
Jacksonville, Florida, United States | |
Orange City, Florida, United States | |
Winter Park, Florida, United States | |
United States, Georgia | |
Atlanta, Georgia, United States | |
Augusta, Georgia, United States | |
United States, Iowa | |
Iowa City, Iowa, United States | |
United States, Maryland | |
Baltimore, Maryland, United States | |
United States, Michigan | |
Ann Arbor, Michigan, United States | |
Southfield, Michigan, United States | |
United States, New Jersey | |
Morristown, New Jersey, United States | |
United States, New York | |
Armonk, New York, United States | |
United States, North Carolina | |
Hickory, North Carolina, United States | |
United States, Ohio | |
Canton, Ohio, United States | |
United States, Pennsylvania | |
Hazelton, Pennsylvania, United States | |
Hershey, Pennsylvania, United States | |
United States, South Carolina | |
Charleston, South Carolina, United States | |
United States, South Dakota | |
Sioux Falls, South Dakota, United States | |
United States, Texas | |
San Antonio, Texas, United States |
Study Director: | William V Williams, MD | Incyte Corporation |
Responsible Party: | Incyte Corporation |
ClinicalTrials.gov Identifier: | NCT01445769 History of Changes |
Other Study ID Numbers: |
18424-261 |
First Posted: | October 4, 2011 Key Record Dates |
Results First Posted: | September 19, 2014 |
Last Update Posted: | September 19, 2014 |
Last Verified: | September 2014 |
Keywords provided by Incyte Corporation:
Myelofibrosis Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis PMF PPV-MF |
PET-MF Open label Ruxolitinib 18424 Jak inhibitor |
Additional relevant MeSH terms:
Primary Myelofibrosis Polycythemia Polycythemia Vera Thrombocytosis Thrombocythemia, Essential Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
Bone Marrow Neoplasms Hematologic Neoplasms Neoplasms by Site Neoplasms Blood Platelet Disorders Blood Coagulation Disorders Hemorrhagic Disorders |