Back to resultsA Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Primary Purpose
MPN (Myeloproliferative Neoplasms)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Parsaclisib
Parsaclisib
Ruxolitinib
Parsaclisib
Parsaclisib
Sponsored by
About this trial
This is an interventional treatment trial for MPN (Myeloproliferative Neoplasms) focused on measuring 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
Eligibility 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
Sites / Locations
- Birmingham Hematology & Oncolgy Associates Llc
- Mayo Clinic Arizona
- Alta Bates Medical Center
- City of Hope National Medical Center
- California Cancer Associates For Research and Excellence
- University of Southern California
- UCLA School of Medicine
- Pcr Oncology
- California Cancer Assoc. for Research and Excellence
- Georgetown University Hospital
- Shands Hospital
- Emory University
- University of Chicago Medical Center
- Indiana Blood and Marrow Transplantation
- McFarland Clinic
- University of Kansas Cancer Center
- Norton Cancer Institute
- Saint Agnes Hospital
- Cancer Center For Blood Disorders
- Massachusetts General Hospital
- Washington University School of Medicine
- Summit Medical Group
- Hackensack University Medical Center
- New Mexico Cancer Care Alliance
- Montefiore Medical Center
- Roswell Park Cancer Institute
- Mount Sinai School of Medicine
- Columbia University Medical Center
- Memorial Sloan Kettering Cancer Center
- Oncology Hematology Care, Inc.
- Cleveland Clinic
- Oregon Health & Science University
- Rush University Medical Center
- Baylor Scott and White Research Institute
- Md Anderson Cancer Center
- Cancer Care Centers of South Texas
- Renovatio Clinical Consultants Llc
- Va Salt Lake City Health Care System
- Vista Oncology Inc Ps
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part 1: Ruxolitinib + Parsaclisib
Part 2: Ruxolitinib + Parsaclisib
Part 3: Ruxolitinib + Parsaclisib
Part 4: Ruxolitinib + Parsaclisib
Arm Description
Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.
Part 2 will compare 2 doses of parsaclisib .
Part 3 will compare 2 different long term dosing strategies.
Part 4 will compare 2 different daily dosing strategies.
Outcomes
Primary Outcome Measures
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Part 2, Part 3 and Part 4: Change From Baseline in Spleen Volume at Week 12 as measured by MRI or CT scan
Secondary Outcome Measures
Number of subjects with adverse events (AEs) and changes in vital signs, ECGs, and laboratory parameters
Change in total symptom score as measured by patient-reported myelofibrosis symptoms
Change From Baseline in Spleen Volume at Week 24 as measured by MRI or CT scan
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02718300
Brief Title
A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Official Title
A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
February 8, 2017 (Actual)
Primary Completion Date
January 28, 2021 (Actual)
Study Completion Date
April 29, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MPN (Myeloproliferative Neoplasms)
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Ruxolitinib + Parsaclisib
Arm Type
Experimental
Arm Description
Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.
Arm Title
Part 2: Ruxolitinib + Parsaclisib
Arm Type
Experimental
Arm Description
Part 2 will compare 2 doses of parsaclisib .
Arm Title
Part 3: Ruxolitinib + Parsaclisib
Arm Type
Experimental
Arm Description
Part 3 will compare 2 different long term dosing strategies.
Arm Title
Part 4: Ruxolitinib + Parsaclisib
Arm Type
Experimental
Arm Description
Part 4 will compare 2 different daily dosing strategies.
Intervention Type
Drug
Intervention Name(s)
Parsaclisib
Other Intervention Name(s)
INCB050465
Intervention Description
Up to 3 oral once a day (QD) doses of parsaclisib. Doses will be taken once daily for 8 weeks, followed by once weekly dosing at the same dose level.
Intervention Type
Drug
Intervention Name(s)
Parsaclisib
Other Intervention Name(s)
INCB050465
Intervention Description
Two recommended oral QD doses of parsaclisib. Once daily doses of parsaclisib will be taken for 8 weeks, followed by once weekly dosing at the same dose level.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi®
Intervention Description
The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.
Intervention Type
Drug
Intervention Name(s)
Parsaclisib
Other Intervention Name(s)
INCB050465
Intervention Description
20 mg oral QD dose of parsaclisib for 8 weeks. After 8 weeks patients will take either 20 mg once weekly or 5 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Parsaclisib
Other Intervention Name(s)
INCB050465
Intervention Description
2 dose strategies will be compared:
5 mg parsaclisib beginning on Day 1 until end of treatment.
20 mg oral QD dose of parsaclisib for 8 weeks; after 8 weeks patients will take 5 mg once daily.
Primary Outcome Measure Information:
Title
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame
Baseline to Day 28
Title
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 Measure Information:
Title
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
Title
Change in total symptom score as measured by patient-reported myelofibrosis symptoms
Time Frame
Baseline through Week 12 or Week 24
Title
Change From Baseline in Spleen Volume at Week 24 as measured by MRI or CT scan
Time Frame
Baseline to Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Assad, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Birmingham Hematology & Oncolgy Associates Llc
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35223
Country
United States
Facility Name
Mayo Clinic Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Alta Bates Medical Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
California Cancer Associates For Research and Excellence
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Pcr Oncology
City
Pismo Beach
State/Province
California
ZIP/Postal Code
93449
Country
United States
Facility Name
California Cancer Assoc. for Research and Excellence
City
San Marcos
State/Province
California
ZIP/Postal Code
92069
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana Blood and Marrow Transplantation
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
McFarland Clinic
City
Ames
State/Province
Iowa
ZIP/Postal Code
50010
Country
United States
Facility Name
University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Saint Agnes Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Cancer Center For Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Facility Name
Summit Medical Group
City
Florham Park
State/Province
New Jersey
ZIP/Postal Code
07932
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
New Mexico Cancer Care Alliance
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Oncology Hematology Care, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45230
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Rush University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Baylor Scott and White Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Md Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Cancer Care Centers of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Renovatio Clinical Consultants Llc
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77380
Country
United States
Facility Name
Va Salt Lake City Health Care System
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Vista Oncology Inc Ps
City
Olympia
State/Province
Washington
ZIP/Postal Code
98506
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
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