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)

Myelofibrosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01317875
• Other study ID #: CINC424A2201
• Status: Completed
• Phase: Phase 1
• Start date: March 31, 2011
• Est. completion date: December 31, 2019

Study information

• Verified date: January 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myelofibrosis
• Polycythemia
• Primary Myelofibrosis

Intervention

Drug:
• Ruxolitinib
Starting dose of ruxolitinib for cohort 1 in dose escalation phase - 5mg twice a day (BID) Doses will be increased a total of approximately 5mg for successive dosing cohorts based on baseline platelet count

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Novartis

Countries where clinical trial is conducted

United States,  Austria,  China,  France,  Germany,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities	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).	28 days
Secondary	Number of Treatment Emergent Adverse Events (TEAE's)	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	approximately 4 years
Secondary	Number of Subjects Achieving = 50% Reduction in Palpable Spleen Length	Participants achieving = 50% reduction in palpable spleen length relative to study day 1 by treatment and stratum	24 weeks
Secondary	Change in Spleen Length as Measure by Palpation Over Time	Defined as measurement of change in spleen length by palpation from baseline	Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092
Secondary	PK- C Reactive Protein Levels by PK Quartile (AUC0-12)	To define the PK and C Reactive Protein relationship using PK Quartiles (AUC 0-12, ng*h/mL)	24 weeks
Secondary	PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12)	To define the PK and Interleukin 1 Receptor Antagonist relationship relationship using PK Quartiles (AUC 0-12, ng*h/mL)	24 weeks
Secondary	PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12)	To define the PK and Tissue Necrosis Factor Receptor 2 relationship using PK Quartiles (AUC 0-12, ng*h/mL)	24 weeks
Secondary	AUC 0-Inf	Area Under the Serum Concentration Versus Time Curve,Time 0 to Infinity	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