Clinical trial NCT00509899: Open Label Ruxolitinib (INCB018424) in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis
Official title: A Phase 1/2, Open-Label Study of the JAK2 Inhibitor INCB018424 Administered Orally to Patients With Primary Myelofibrosis (PMF) and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Post-PV/ET)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Myelofibrosis
Polycythemia Vera
Thrombocytosis
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2007-08-01
Enrollment: 154
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 determine the safety, tolerability and effectiveness of ruxolitinib (INCB018424), administered orally to patients with Primary Myelofibrosis (PMF), Post Polycythemia Vera Myelofibrosis (PPV-MF) and Essential Thrombocythemia Myelofibrosis (PET-MF).

Detailed description: This is a multicenter, open-label, non-randomized, dose escalation study of ruxolitinib, a small molecule Janus kinase (JAK) inhibitor, administered orally to patients with PMF, PPEV-MF or PET-MF. The study is comprised of 3 parts:

Part 1: Dose escalation and determination of maximum tolerated dose (complete).

Part 2: Exploration of alternative dosing schedules (complete).

Part 3: Further evaluation of selected dose regimens, including additional response measures to explore effect of ruxolitinib on symptoms and other parameters including daily physical activity and long-term survival (ongoing).

Eligibility criteria: Inclusion Criteria:

* Diagnosed with PMF or Post-PV/ET MF
* Patients with myelofibrosis requiring therapy
* Adequate bone marrow reserve

Exclusion Criteria:

* Received anti-cancer medications or investigational therapy in the past 14 days

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From Baseline to the interim clinical cut-off date (31 December 2009). The median time on study was 14.8 months, with a range of 26 days to 29.7 months. As of March 1, 2011 the total exposure to ruxolitinib was 269 patient-years.
measure: Percentage of Participants With Clinical Improvement (CI) Over Time
timeFrame: Week 12, 24, 36, 48 and 60
Secondary outcomes:
measure: Percentage of Participants Achieving ≥ 50% Reduction From Baseline in Spleen Palpation Length Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 24, 36, 48 and 60
measure: Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume Over Time
timeFrame: Baseline, Weeks 4, 12, 24 and 48
measure: Change From Baseline in Myelofibrosis Total Symptom Score at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Health-Related Quality of Life
timeFrame: Baseline and Week 24
measure: Change From Baseline in Body Weight Over Time
timeFrame: Baseline and Weeks 4, 8, 12, 24, 36, 48 and 60.
measure: Change From Baseline to Week 24 in Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Rochester
country: United States
state: Minnesota
city: Houston
country: United States
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center, Houston, TX
name: Srdan Verstovsek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic, Rochester, MN
name: Ayalew Tefferi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010 Sep 16;363(12):1117-27. doi: 10.1056/NEJMoa1002028.
citation: Verstovsek S, Kantarjian HM, Estrov Z, Cortes JE, Thomas DA, Kadia T, Pierce S, Jabbour E, Borthakur G, Rumi E, Pungolino E, Morra E, Caramazza D, Cazzola M, Passamonti F. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood. 2012 Aug 9;120(6):1202-9. doi: 10.1182/blood-2012-02-414631. Epub 2012 Jun 20.
citation: Kvasnicka HM, Thiele J, Bueso-Ramos CE, Sun W, Cortes J, Kantarjian HM, Verstovsek S. Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis. J Hematol Oncol. 2018 Mar 15;11(1):42. doi: 10.1186/s13045-018-0585-5.