A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis - Full Text View

Purpose

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	Intervention	Phase
Myelofibrosis	Drug: INCB050465 Drug: Ruxolitinib	Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial. More info ...


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

Genetics Home Reference related topics: primary myelofibrosis

Drug Information available for: Ruxolitinib Ruxolitinib phosphate

Genetic and Rare Diseases Information Center resources: Myelofibrosis Polycythemia Vera Chronic Myeloproliferative Disorders Essential Thrombocythemia

U.S. FDA Resources

Further study details as provided by Incyte Corporation:

Primary Outcome Measures:

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline to Day 28 ]
Part 2: 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:

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 ]
Change in total symptom score as measured by patient-reported myelofibrosis symptoms [ Time Frame: Baseline through Week 12 or Week 24 ]
Change From Baseline in Spleen Volume at Week 24 as measured by MRI or CT scan [ Time Frame: Baseline to Week 24 ]


Estimated Enrollment:	78
Study Start Date:	June 2016
Estimated Study Completion Date:	June 2019
Estimated Primary Completion Date:	September 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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®

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02718300

Contacts


Contact: Incyte Corporation Call Center	1.855.463.3463

Show 27 Study Locations

Sponsors and Collaborators

Incyte Corporation

Investigators


Study Director:	Albert Assad, MD	Incyte Corporation

More Information


Responsible Party:	Incyte Corporation
ClinicalTrials.gov Identifier:	NCT02718300 History of Changes
Other Study ID Numbers:	INCB 50465-201
Study First Received:	March 21, 2016
Last Updated:	July 27, 2017

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

ClinicalTrials.gov processed this record on September 21, 2017