Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ruxolitinib (INCB018424) in Participants With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia-myelofibrosis and Post Polycythemia Vera-myelofibrosis (PPV-MF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01348490
Recruitment Status : Completed
First Posted : May 5, 2011
Results First Posted : January 28, 2020
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

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.

Condition or disease Intervention/treatment Phase
MPN (Myeloproliferative Neoplasms) Drug: Ruxolitinib Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 15, 2011
Actual Primary Completion Date : December 19, 2018
Actual Study Completion Date : December 19, 2018


Arm Intervention/treatment
Experimental: Ruxolitinib 5 mg
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.
Drug: Ruxolitinib
Ruxolitinib (INCB018424), 5 mg bid
Other Name: INCB018424




Primary Outcome Measures :
  1. Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose [ Time Frame: Baseline and Week 24 ]
    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.

  2. 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 [ Time Frame: Baseline and Week 24 ]
    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.

  3. Percentage of Participants With Treatment-emergent Adverse Events (TEAE) [ Time Frame: Up to Week 156 ]

    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.


  4. 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) [ Time Frame: Up to Week 156 ]

    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.


  5. Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 [ Time Frame: Up to Week 156 ]

    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 :
  1. Percent Change in Spleen Volume at Week 24 Compared to Baseline [ Time Frame: Baseline and Week 24 ]
    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.

  2. Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline [ Time Frame: Baseline and Week 24 ]
    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..

  3. Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline [ Time Frame: Baseline and Week 24 ]
    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.

  4. Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline [ Time Frame: Baseline and Week 24 ]
    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.

  5. 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 [ Time Frame: Baseline and Week 24 ]
    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.

  6. Change in Spleen Length Measured by Palpation [ Time Frame: Up to Week 156 ]
    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.

  7. Percent Change From Baseline in Spleen Length Measured by Palpation [ Time Frame: Up to Week 156 ]
    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.

  8. Patient Global Impression of Change (PGIC) Score at Each Visit [ Time Frame: Up to Week 156 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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): NCT01348490


Locations
Layout table for location information
United States, Alabama
Birmingham, Alabama, United States
United States, California
Beverly Hills, California, United States
Burbank, California, United States
La Jolla, California, United States
Los Angeles, California, United States
Pomona, California, United States
San Diego, California, United States
United States, Connecticut
New Haven, Connecticut, United States
United States, Florida
Fort Myers, Florida, United States
Jacksonville, Florida, United States
Orange City, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Augusta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Louisiana
New Orleans, Louisiana, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Michigan
Ann Arbor, Michigan, United States
Southfield, Michigan, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, New Jersey
Hackensack, New Jersey, United States
Morristown, New Jersey, United States
Somerville, New Jersey, United States
United States, New York
New York, New York, United States
United States, North Carolina
Durham, North Carolina, United States
Hickory, North Carolina, United States
United States, Ohio
Canton, Ohio, United States
Cleveland, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Danville, Pennsylvania, United States
Hershey, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Houston, Texas, United States
San Antonio, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Vermont
Burlington, Vermont, United States
Sponsors and Collaborators
Incyte Corporation
Investigators
Layout table for investigator information
Study Director: Peter Langmuir, MD Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:
Study Protocol  [PDF] August 9, 2013
Statistical Analysis Plan  [PDF] January 17, 2012


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT01348490    
Other Study ID Numbers: INCB18424-258
First Posted: May 5, 2011    Key Record Dates
Results First Posted: January 28, 2020
Last Update Posted: January 28, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
PMF
PPV-MF
PET-MF
Additional relevant MeSH terms:
Layout table for MeSH terms
Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Myeloproliferative Disorders
Thrombocytosis
Thrombocythemia, Essential
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders