Clinical trial NCT02718300: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2016-03-24
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: up to Day 28
measure: Change From Baseline in Spleen Volume Through Week 12 of the Initial Study Period as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants)
timeFrame: Baseline; Week 12
Secondary outcomes:
measure: Change From Baseline in Spleen Volume Through Week 24 of the Initial Study Period as Measured by MRI (or CT Scan in Applicable Participants)
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants )
timeFrame: Baseline; Week 24
measure: Change From Baseline in the Total Symptom Score (TSS) Through Week 12 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) Version 3.0 (v3.0) Symptom Diary
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary
timeFrame: Baseline; Week 12
measure: Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
timeFrame: Baseline; Week 24
measure: Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
timeFrame: Baseline; Week 12
measure: Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF
timeFrame: Baseline; Week 12
measure: Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
timeFrame: Baseline; Week 24
measure: Number of Participants With the Indicated Patient Global Impression of Change (PGIC) Score at Week 12, Week 24, and the End of Treatment (EOT)
timeFrame: Baseline; up to 1494 days (EOT)
measure: Mean PGIC Score at Week 12, Week 24, and the EOT
timeFrame: up to 1494 days (EOT)
measure: Best Overall Response (Percentage of Participants With Complete Response [CR] or Partial Response [PR]) for Investigator-Reported International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Response Assessment
timeFrame: Week 12 and every 12 weeks thereafter (up to 1494 days [EOT])
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to approximately 4 years
measure: Number of Participants With Any TEAE During the Transition Period
timeFrame: up to approximately 4 years
measure: Cmax of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Tmax of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Cmin of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: AUC0-4h of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: AUC0-t of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Clast of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Tlast of Parsaclisib
timeFrame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Cmax of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Tmax of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Cmin of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: AUC0-4h of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: AUC0-t of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Clast of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
measure: Tlast of Ruxolitinib
timeFrame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Hematology & Oncolgy Associates Llc
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Fresno
country: United States
facility: California Cancer Associates For Research and Excellence
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: Pismo Beach
country: United States
facility: Pcr Oncology
state: California
city: San Marcos
country: United States
facility: California Cancer Assoc. for Research and Excellence
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: Saint Agnes Hospital
state: Maryland
city: Bethesda
country: United States
facility: Cancer Center For Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Rush University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical Consultants Llc
state: Texas
city: Salt Lake City
country: United States
facility: Va Salt Lake City Health Care System
state: Utah
city: Olympia
country: United States
facility: Vista Oncology Inc Ps
state: Washington
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, MD
role: STUDY_DIRECTOR
References: