An Open-label Assessment of Once-daily Dosing of a Sustained Release (SR) Formulation of INCB018424 in Patients With Primary Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, and Post-polycythemia Vera Myelofibrosis
Overview
- Phase
- Phase 2
- Intervention
- Ruxolitinib
- Conditions
- Myelofibrosis
- Sponsor
- Incyte Corporation
- Enrollment
- 41
- Primary Endpoint
- Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to determine the safety and tolerability of ruxolitinib (INCB018424) sustained release (SR) formulation in participants with primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF), and post-essential thrombocythemia MF (PET-MF).
Detailed Description
The study will enroll approximately 40 participants with PMF, PPV-MF or PET-MF. Participants will take ruxolitinib SR once daily for 16 consecutive weeks and then transition to a comparable twice daily dose regimen of ruxolitinib using the immediate release (IR) tablets which have been under investigation in controlled Phase 1, 2, and 3 clinical trials. Participants receiving benefit from treatment with ruxolitinib may continue further participation with IR tablets up to the time when the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier. Follow-up will occur at least 30 days following the last dose of ruxolitinib.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants 18 years of age or older.
- •Participants must be diagnosed with primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (PPV-MF), or post-polycythemia vera myelofibrosis (PET-MF).
- •Participants with myelofibrosis requiring therapy must be classified as high risk (3 or more prognostic factors), intermediate risk level 2 (2 prognostic factors), or intermediate risk level 1 (1 prognostic factor)defined by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT).
- •Participants must have a palpable spleen measuring 5 cm or greater below the costal margin.
Exclusion Criteria
- •Participants with a life expectancy of less than 6 months.
- •Participants of childbearing potential who are unwilling to take appropriate precautions to avoid pregnancy or fathering a child.
- •Participants with inadequate bone marrow reserve.
- •Participants with history of platelet counts \< 50,000/μL, platelet transfusion(s), or an absolute neutrophil count \< 500/μL in the month prior to Screening.
- •Participants with inadequate liver or renal function at Screening and Baseline visits.
Arms & Interventions
Ruxolitinib 25 mg SR/10, 15, or 20 mg IR
Participants began administration with 25 mg ruxolitinib sustained release (SR) once daily (QD). After 8 weeks, if there was inadequate efficacy, the dose level could be titrated to 50 mg SR QD or 25 mg SR every other day (QOD) alternating with 50 mg SR QOD. At Week 16, participants transitioned to ruxolitinib 10, 15, or 20 mg immediate release (IR) orally twice daily. Participants who continued to demonstrate benefit in the opinion of the investigator could remain on ruxolitinib IR until the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier; the dose received was based on platelet counts at the time of transition.
Intervention: Ruxolitinib
Outcomes
Primary Outcomes
Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16
Time Frame: Baseline to Week 16
Overall Response (OR) at Week 16
Time Frame: Baseline to Week 16
The investigator graded OR according to the International Working Group for Myelofibrosis Research and Therapy criteria for treatment response. As bone marrow biopsies were not taken after baseline, the best achievable response was clinical improvement which required 1 of the following in the absence of progressive disease (PD): (1) A ≥ 2 g/dL increase in hemoglobin level or (2) either a palpable ≥ 50% reduction of splenomegaly of a spleen ≥ 10 cm at baseline or a spleen palpable at \> 5 cm at baseline becoming not palpable. PD required 1 of the following: (1) Progressive splenomegaly defined by the appearance of previously absent splenomegaly that was palpable at \> 5 cm below the left costal margin or a ≥ 100% increase in palpable distance for baseline splenomegaly of 5-10 cm or a ≥ 50% increase in palpable distance for baseline splenomegaly of \> 10 cm or (2) an increase in peripheral blood blast percentage to ≥ 20% that lasted for ≥ 8 weeks. Stable disease: None of the above.
Secondary Outcomes
- Change From Baseline in Spleen Volume at Week 16(Baseline to Week 16)
- Change From Baseline in Spleen Length at Week 16(Baseline to Week 16)
- Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 16 From Baseline(Baseline to Week 16)
- Change From Baseline in the Total Symptom Score at Week 16(Baseline to Week 16)
- Percentage of Participants With a ≥ 50% Reduction From Baseline in the Total Symptom Score at Week 16(Baseline to Week 16)
- Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib 25 mg SR on Day 1(Day 1)
- Time to Reach the Maximum Plasma Concentration (Tmax) of Ruxolitinib 25 mg SR on Day 1(Day 1)
- Area Under the Plasma Concentration-time Curve (AUC) of Ruxolitinib 25 mg SR on Day 1(Day 1)