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A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

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ClinicalTrials.gov Identifier: NCT02718300
Recruitment Status : Recruiting
First Posted : March 24, 2016
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Study Description
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Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of INCB050465 and ruxolitinib in subjects with myelofibrosis.

Condition or disease Intervention/treatment Phase
MPN (Myeloproliferative Neoplasms) Drug: INCB050465 Drug: Ruxolitinib Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Study Start Date : June 2016
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Ruxolitinib + INCB050465
Initial cohort dose of INCB050465 added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.
 Drug: INCB050465
Up to 3 oral once a day (QD) doses of INCB050465. Doses will be taken once daily for 8 weeks, followed by once weekly dosing at the same dose level.

Drug: Ruxolitinib
The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of INCB050465.
Other Name: Jakafi®
Experimental: Part 2: Ruxolitinib + INCB050465
Part 2 will compare 2 doses of INCB050465.
 Drug: INCB050465
Two recommended oral QD doses of INCB050465. Once daily doses of INCB050465 will be taken for 8 weeks, followed by once weekly dosing at the same dose level.

Drug: Ruxolitinib
The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of INCB050465.
Other Name: Jakafi®
Experimental: Part 3: Ruxolitinib + INCB050465
Part 3 will compare 2 different long term dosing strategies.
 Drug: Ruxolitinib
The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of INCB050465.
Other Name: Jakafi®

Drug: INCB050465
20 mg oral QD dose of INCB050465 for 8 weeks. After 8 weeks patients will take either 20 mg once weekly or 5 mg once daily.
Experimental: Part 4: Ruxolitinib + INCB050465
Part 4 will compare 2 different daily dosing strategies.
 Drug: Ruxolitinib
The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of INCB050465.
Other Name: Jakafi®

Drug: INCB050465

2 dose strategies will be compared:

  1. 5 mg INCB050465 beginning on Day 1 until end of treatment.
  2. 20 mg oral QD dose of INCB050465 for 8 weeks; after 8 weeks patients will take 5 mg once daily.


Outcome Measures
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Primary Outcome Measures :
  1. Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline to Day 28 ]
  2. Part 2, Part 3 and Part 4: Change From Baseline in Spleen Volume at Week 12 as measured by MRI or CT scan [ Time Frame: Baseline to Week 12 ]

Secondary Outcome Measures :
  1. Number of subjects with adverse events (AEs) and changes in vital signs, ECGs, and laboratory parameters [ Time Frame: Screening through up to 30 days after last dose of study drug, up to 25 months ]
  2. Change in total symptom score as measured by patient-reported myelofibrosis symptoms [ Time Frame: Baseline through Week 12 or Week 24 ]
  3. Change From Baseline in Spleen Volume at Week 24 as measured by MRI or CT scan [ Time Frame: Baseline to Week 24 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis
  • Palpable spleen of > 10 cm below the left subcostal margin on physical examination at the screening visit OR
  • Palpable splenomegaly of 5 to 10 cm below left subcostal margin on physical exam AND active symptoms of MF at the screening visit as demonstrated by presence of 1 symptom score ≥ 5 or 2 symptom scores ≥ 3 using the Screening Symptom Form
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

  • Use of experimental drug therapy for myelofibrosis, or any other standard drug (eg, danazol, hydroxyurea, etc) with the exception of ruxolitinib within 6 months of starting study (combination) therapy and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better
  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications
  • Unwillingness to be transfused with blood components

  • Recent history of inadequate bone marrow reserve as demonstrated by the following:

    • Platelet count < 50 × 10^9/L in the 4 weeks before screening or platelet transfusion(s) within 8 weeks before screening
    • Absolute neutrophil count levels < 0.5 × 10^9/L in the 4 weeks before screening
    • Subjects with peripheral blood blast count of > 10% at the screening or baseline hematology assessments
    • Subjects who are not willing to receive red blood cell (RBC) transfusions to treat low hemoglobin levels

  • Inadequate liver function at screening as demonstrated by the following:

    • Direct bilirubin ≥ 2.0 × the upper limit of laboratory normal (ULN). (NOTE: direct bilirubin will only be determined if total bilirubin is ≥ 2.0 × ULN)
    • alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN
  • Inadequate renal function at screening as demonstrated by creatinine clearance < 50 mL/min or glomerular filtration rate < 50 mL/min/1.73 m^2
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02718300


Contacts
Contact: Incyte Corporation Call Center 1.855.463.3463

  Show 24 Study Locations
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Albert Assad, MD Incyte Corporation
More Information
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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02718300     History of Changes
Other Study ID Numbers: INCB 50465-201
First Posted: March 24, 2016    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018

Keywords provided by Incyte Corporation:
Primary myelofibrosis (PMF)
post-polycythemia vera myelofibrosis (PPV-MF)
post-essential thrombocythemia myelofibrosis (PET-MF)
 myeloproliferative neoplasms (MPNs)
phosphoinositide 3-kinase (PI3K) inhibitor
Janus kinase (JAK) inhibitor

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases