Clinical trial NCT01317875: Study of the JAK Inhibitor Ruxolitinib Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera-Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia-Myelofibrosis (PET-MF)
Official title: A Phase Ib, Open-label, Dose-finding Study of the JAK Inhibitor INC424 Tablets Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-polycythemia Veramyelofibrosis (PPV-MF) or Post-essentialthrombocythemia-myelofibrosis (PET-MF) and Baseline Platelet Counts ≥50 x109/L and <100 x109/L (EXPAND)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelofibrosis
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2011-03-17
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase IB, open-label, dose-finding study of the JAK 1 and 2 inhibitor ruxolitinib in patients with myelofibrosis (MF). The study consists of two periods: the core study period, comprising the dose escalation stage and the safety extension phase up to Week 24, then the extension study period beyond Week 24 and up to 3 years, to further characterize the safety and efficacy of ruxolitinib in this patient population. The dose escalation phase will enroll successive cohorts of patients who receive increasing doses of ruxolitinib until the maximum safe starting dose (MSSD) is determined. In the safety expansion phase, additional patients will be treated with ruxolitinib at the MSSD defined during dose escalation. The primary objective is to establish the MSSD of ruxolitinib in patients with MF and starting platelet counts \< 100 x 10 \^9/L


Eligibility criteria: Inclusion Criteria:

* Require treatment for MF and classified at least as intermediate risk level 1 defined by the International Working Group.
* Platelet count \< 100x10 \^9/L at screening or at Study Day 1.

Exclusion Criteria:

* Received platelet transfusion within 14 days prior to Screening evaluations.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Number of Treatment Emergent Adverse Events (TEAE's)
timeFrame: approximately 4 years
measure: Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length
timeFrame: 24 weeks
measure: Change in Spleen Length as Measure by Palpation Over Time
timeFrame: Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092
measure: PK- C Reactive Protein Levels by PK Quartile (AUC0-12)
timeFrame: 24 weeks
measure: PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12)
timeFrame: 24 weeks
measure: PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12)
timeFrame: 24 weeks
measure: AUC 0-Inf
timeFrame: 0.25 to 0.75, 1 to 3, and 4 to 12 hours postdose on Day 1 and predose, 0.25 to 0.75 hours, and 1 to 3 hours postdose on Day 15, with a random sample on Days 29 and 57
Other outcomes:
Locations:
city: Winter Park
country: United States
state: Florida
city: Baltimore
country: United States
state: Maryland
city: Houston
country: United States
state: Texas
city: Vienna
country: Austria
city: Nanjing
country: China
state: Jiangsu
city: Chengdu
country: China
state: Sichuan
city: Hangzhou
country: China
state: Zhejiang
city: Beijing
country: China
city: Angers
country: France
city: Paris
country: France
city: Pierre-Benite
country: France
city: Leipzig
country: Germany
city: Firenze
country: Italy
city: Milano
country: Italy
city: Terni
country: Italy
city: Rotterdam
country: Netherlands
city: Belfast
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Incyte Corporation
name: Mark Jones, MD
role: STUDY_DIRECTOR
References:
citation: Guglielmelli P, Kiladjian JJ, Vannucchi AM, Duan M, Meng H, Pan L, He G, Verstovsek S, Boyer F, Barraco F, Niederwieser D, Pungolino E, Liberati AM, Harrison C, Roussou P, Wroclawska M, Karumanchi D, Sinclair K, Te Boekhorst PAW, Gisslinger H. Efficacy and safety of ruxolitinib in patients with myelofibrosis and low platelet count (50 x 109/L to <100 x 109/L) at baseline: the final analysis of EXPAND. Ther Adv Hematol. 2022 Sep 10;13:20406207221118429. doi: 10.1177/20406207221118429. eCollection 2022.