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

NCT01348490 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: INCB18424-258
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 38

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.

Conditions

MPN (Myeloproliferative Neoplasms)

Keywords

PMF; PPV-MF; PET-MF

Outcome Measures

Primary Outcomes (5)

• 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.

  Baseline and Week 24

• 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.

  Baseline and Week 24

• 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.

  Up to Week 156

• 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.

  Up to Week 156

• 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.

  Up to Week 156

Secondary Outcomes (8)

• Percent Change in Spleen Volume at Week 24 Compared to Baseline

  Baseline and Week 24

• Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline

  Baseline and Week 24

• Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline

  Baseline and Week 24

• Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline

  Baseline and Week 24

• 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

  Baseline and Week 24

Study Arms (1)

Ruxolitinib 5 mg

EXPERIMENTAL

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

Interventions

Ruxolitinib DRUG

Ruxolitinib (INCB018424), 5 mg bid

Also known as: INCB018424

Ruxolitinib 5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (38)

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Birmingham, Alabama, United States

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Beverly Hills, California, United States

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Burbank, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Pomona, California, United States

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San Diego, California, United States

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New Haven, Connecticut, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Orange City, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Chicago, Illinois, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Ann Arbor, Michigan, United States

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Southfield, Michigan, United States

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St Louis, Missouri, United States

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Hackensack, New Jersey, United States

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Morristown, New Jersey, United States

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Somerville, New Jersey, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Hickory, North Carolina, United States

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Canton, Ohio, United States

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Cleveland, Ohio, United States

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Portland, Oregon, United States

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Danville, Pennsylvania, United States

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Hershey, Pennsylvania, United States

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Charleston, South Carolina, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Burlington, Vermont, United States

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Related Publications (2)

• 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.

  PMID: 34911667 DERIVED

• 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.

  PMID: 24283202 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Participants with platelet counts of 50 to 100 x 10\^9/L were enrolled to begin ruxolitinib at 5 mg BID. Subjects could then titrate their dose to an dose that offers benefit. Only the overall data was calculated for the Participant and Baseline data.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Peter Langmuir, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 5, 2011
• Study Start: June 15, 2011
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: January 28, 2020
• Results First Posted: January 28, 2020

Record last verified: 2020-01

Locations

US (38)