Clinical trial NCT01348490: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: MPN (Myeloproliferative Neoplasms)
Keywords: PMF
PPV-MF
PET-MF
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2011-05-05
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose
timeFrame: Baseline and Week 24
measure: 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
timeFrame: Baseline and Week 24
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: Up to Week 156
measure: 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)
timeFrame: Up to Week 156
measure: Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03
timeFrame: Up to Week 156
Secondary outcomes:
measure: Percent Change in Spleen Volume at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: 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
timeFrame: Baseline and Week 24
measure: Change in Spleen Length Measured by Palpation
timeFrame: Up to Week 156
measure: Percent Change From Baseline in Spleen Length Measured by Palpation
timeFrame: Up to Week 156
measure: Patient Global Impression of Change (PGIC) Score at Each Visit
timeFrame: Up to Week 156
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Beverly Hills
country: United States
state: California
city: Burbank
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Pomona
country: United States
state: California
city: San Diego
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Fort Myers
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Orange City
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Southfield
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Hackensack
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: Somerville
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Danville
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Burlington
country: United States
state: Vermont
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir, MD
role: STUDY_DIRECTOR
References:
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.
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.