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)

Phase 1

Completed

• Conditions: Myelofibrosis
• Interventions: Drug: Ruxolitinib

• Registration Number: NCT01317875
• Lead Sponsor: Incyte Corporation

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-03-14
• Study First Submitted QC: 2011-03-16
• Study First Posted: 2011-03-17
• Study Start: 2011-03-31
• Primary Completion: 2019-12-31
• Study Completion: 2019-12-31
• Results First Submitted: 2020-12-26
• Status Verified: 2022-01
• Results First Submitted QC: 2022-01-10
• Last Update Submitted: 2022-01-10
• Results First Posted: 2022-03-09
• Last Update Posted: 2022-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

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.

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stratum -1	Ruxolitinib	Participants with baseline Platelet counts of 75-99 x10\^9/L
Stratum -2	Ruxolitinib	Participants with baseline Platelet counts of 50-74 x10\^9/L

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities	28 days	DLT was defined as the occurrence of any of the following treatment-related toxicities, occurring through Day 28: Any grade ≥ 2 hemorrhagic event ; Any grade thrombocytopenia requiring PLT transfusion; PLT count \< 25x109/L\*; Grade 4 neutropenia (absolute neutrophil count \< 0.5x109/L)\*; Grade ≥ 3 febrile neutropenia\*; Grade ≥ 2 total serum bilirubin with coincident direct bilirubin ≥ 0.5 mg/dL; Grade 3 non-hematologic toxicity for ≥ 7 consecutive days; Grade 4 non-hematologic toxicity. In the dose escalation stage in the core study period, the starting does in both strata was 5mg bid. Successive cohorts of newly enrolled patients received increasing doses of ruxolitinib until the Maximum Safe Starting Dose (MSSD) was determined. Initially, only patients with PLT counts 75-99 x10\^9/L (stratum 1) were allowed to be enrolled. Once safety was established in stratum 1 at the first 2 dose cohorts, eligible population was further expanded to patients with PLT counts 50-74 x10\^9/L (stratum 2).

Secondary Outcome Measures

Name	Time	Method
PK- C Reactive Protein Levels by PK Quartile (AUC0-12)	24 weeks	To define the PK and C Reactive Protein relationship using PK Quartiles (AUC 0-12, ng\*h/mL)
AUC 0-Inf	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	Area Under the Serum Concentration Versus Time Curve，Time 0 to Infinity
PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12)	24 weeks	To define the PK and Interleukin 1 Receptor Antagonist relationship relationship using PK Quartiles (AUC 0-12, ng\*h/mL)
Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length	24 weeks	Participants achieving ≥ 50% reduction in palpable spleen length relative to study day 1 by treatment and stratum
Change in Spleen Length as Measure by Palpation Over Time	Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092	Defined as measurement of change in spleen length by palpation from baseline
Number of Treatment Emergent Adverse Events (TEAE's)	approximately 4 years	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12)	24 weeks	To define the PK and Tissue Necrosis Factor Receptor 2 relationship using PK Quartiles (AUC 0-12, ng\*h/mL)