A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Overview
- Phase
- Phase 2
- Intervention
- Parsaclisib
- Conditions
- MPN (Myeloproliferative Neoplasms)
- Sponsor
- Incyte Corporation
- Enrollment
- 74
- Locations
- 39
- Primary Endpoint
- Number of Participants With Dose-limiting Toxicities (DLTs)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
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)
Arms & Interventions
Part 1: Ruxolitinib + Parsaclisib
Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.
Intervention: Parsaclisib
Part 1: Ruxolitinib + Parsaclisib
Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria.
Intervention: Ruxolitinib
Part 2: Ruxolitinib + Parsaclisib
Part 2 will compare 2 doses of parsaclisib .
Intervention: Parsaclisib
Part 2: Ruxolitinib + Parsaclisib
Part 2 will compare 2 doses of parsaclisib .
Intervention: Ruxolitinib
Part 3: Ruxolitinib + Parsaclisib
Part 3 will compare 2 different long term dosing strategies.
Intervention: Ruxolitinib
Part 3: Ruxolitinib + Parsaclisib
Part 3 will compare 2 different long term dosing strategies.
Intervention: Parsaclisib
Part 4: Ruxolitinib + Parsaclisib
Part 4 will compare 2 different daily dosing strategies.
Intervention: Ruxolitinib
Part 4: Ruxolitinib + Parsaclisib
Part 4 will compare 2 different daily dosing strategies.
Intervention: Parsaclisib
Outcomes
Primary Outcomes
Number of Participants With Dose-limiting Toxicities (DLTs)
Time Frame: up to Day 28
DLTs were defined as the occurrence of any protocol-defined toxicities occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression, other medications) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria.
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)
Time Frame: Baseline; Week 12
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants)
Time Frame: Baseline; Week 12
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Secondary Outcomes
- Change From Baseline in Spleen Volume Through Week 24 of the Initial Study Period as Measured by MRI (or CT Scan in Applicable Participants)(Baseline; Week 24)
- Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants )(Baseline; Week 24)
- 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(Baseline; Week 12)
- Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary(Baseline; Week 12)
- Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary(Baseline; Week 24)
- Clast of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF(Baseline; Week 12)
- Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF(Baseline; Week 24)
- Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF(Baseline; Week 24)
- Number of Participants With the Indicated Patient Global Impression of Change (PGIC) Score at Week 12, Week 24, and the End of Treatment (EOT)(Baseline; up to 1494 days (EOT))
- Mean PGIC Score at Week 12, Week 24, and the EOT(up to 1494 days (EOT))
- 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(Week 12 and every 12 weeks thereafter (up to 1494 days [EOT]))
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE)(up to approximately 4 years)
- Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary(Baseline; Week 24)
- Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)(Baseline; Week 12)
- Tlast of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Number of Participants With Any TEAE During the Transition Period(up to approximately 4 years)
- Cmax of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Tmax of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Cmin of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- AUC0-4h of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- AUC0-t of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Clast of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Tlast of Parsaclisib(Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Cmax of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Tmax of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)
- Cmin of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)
- AUC0-4h of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)
- AUC0-t of Ruxolitinib(Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose)