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.
Brief Title
A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Categories
Completion Date
Completion Date Type
Actual
Conditions
MPN (Myeloproliferative Neoplasms)
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02718300
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 50465-201
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Participants With Dose-limiting Toxicities (DLTs)
Outcome Time Frame
up to Day 28
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome 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)
Outcome Time Frame
Baseline; Week 12
Outcome Description
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Measure
Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants)
Outcome Time Frame
Baseline; Week 12
Secondary Ids
Secondary Id
Parsaclisib
Secondary Outcomes
Outcome Description
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Outcome Time Frame
Baseline; Week 24
Outcome 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)
Outcome Description
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants )
Outcome Description
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 12 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 12 visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Outcome Time Frame
Baseline; Week 12
Outcome 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
Outcome Description
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 12 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 12 visit. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Time Frame
Baseline; Week 12
Outcome Measure
Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary
Outcome Description
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 24 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 24 visit. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
Outcome Description
The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total scores from the last 7 days before the first dose of INCB050465. The Week 24 TSS was the average of the daily total scores from the last 7 consecutive days before the Week 24 visit. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
Outcome Description
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Outcome Time Frame
Baseline; Week 12
Outcome Measure
Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Outcome Description
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Time Frame
Baseline; Week 12
Outcome Measure
Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF
Outcome Description
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
Outcome Description
The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.
Outcome Time Frame
Baseline; Week 24
Outcome Measure
Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
Outcome Description
The PGIC questionnaire consists of a single question with 7 possible answers: "Since the start of treatment you've received in this study, your myelofibrosis symptoms are: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse."
Outcome Time Frame
Baseline; up to 1494 days (EOT)
Outcome 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)
Outcome Description
The PGIC questionnaire consists of a single question with 7 possible answers: "Since the start of treatment you've received in this study, your myelofibrosis symptoms are: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse."
Outcome Time Frame
up to 1494 days (EOT)
Outcome Measure
Mean PGIC Score at Week 12, Week 24, and the EOT
Outcome Description
A participant was considered as a responder if the participant had a best overall response of CR or PR. CR: (a) bone marrow (BM): age-adjusted normocellularity (AAN); \< 5% blasts; ≤ grade 1 myelofibrosis (MF); (b) peripheral blood (PD): hemoglobin (Hg) ≥ 100 grams per Liter (g/L) and \< upper normal limit (UNL); neutrophils ≥ 1 × 10\^9/L and \< UNL; (c) platelets ≥ 100 × 10\^9/L and \< UNL; \< 2% immature myeloid cells (IMCs); (d) clinical: resolution of disease symptoms; spleen/liver not palpable; no extramedullary hematopoiesis (EMH). PR: (a) PB: Hg ≥ 100 g/L and \< UNL; neutrophils ≥ 1 × 10\^9/L and \< UNL; platelets ≥ 100 × 10\^9/L and \< UNL; \< 2% IMCs; (b) clinical: resolution of disease symptoms; spleen/liver not palpable; no EMH; (c) BM: AAN; \< 5% blasts; ≤ Grade 1 MF; and PB: Hg ≥ 85 g/L but \< 100 g/L and \< UNL; neutrophils ≥ 1 × 10\^9/L and \< UNL; platelets ≥ 50 × 10\^9/L but \< 100 × 10\^9/L and \< UNL; \< 2% IMCs.
Outcome Time Frame
Week 12 and every 12 weeks thereafter (up to 1494 days [EOT])
Outcome 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
Outcome Description
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or requird changes in the study drug(s). TEAEs were defined as AEs that began or worsened from Baseline after the first administration of study drug.
Outcome Time Frame
up to approximately 4 years
Outcome Measure
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Outcome Description
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or requird changes in the study drug(s). TEAEs were defined as AEs that began or worsened from Baseline after the first administration of study drug. Participants who had been assigned to dosing arms with weekly dosing beyond Week 8 had the opportunity to transition to all daily dosing at 5 mg if agreed upon by the participant and the Investigator.
Outcome Time Frame
up to approximately 4 years
Outcome Measure
Number of Participants With Any TEAE During the Transition Period
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Cmax of Parsaclisib
Outcome Description
tmax was defined as the time to the maximum concentration.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Tmax of Parsaclisib
Outcome Description
Cmin was defined as the minimum observed plasma concentration.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Cmin of Parsaclisib
Outcome Description
AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
AUC0-4h of Parsaclisib
Outcome Description
AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
AUC0-t of Parsaclisib
Outcome Description
Clast was defined as the last quantifiable concentration.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Clast of Parsaclisib
Outcome Description
tlast was defined as the time of the last quantifiable concentration.
Outcome Time Frame
Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Tlast of Parsaclisib
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Cmax of Ruxolitinib
Outcome Description
tmax was defined as the time to the maximum concentration.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Tmax of Ruxolitinib
Outcome Description
Cmin was defined as the minimum observed plasma concentration.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Cmin of Ruxolitinib
Outcome Description
AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
AUC0-4h of Ruxolitinib
Outcome Description
AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
AUC0-t of Ruxolitinib
Outcome Description
Clast was defined as the last quantifiable concentration.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Clast of Ruxolitinib
Outcome Description
tlast was defined as the time of the last quantifiable concentration.
Outcome Time Frame
Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Outcome Measure
Tlast of Ruxolitinib
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Swati Goel
Investigator Email
swgoel@montefiore.org
Investigator Phone
718-920-6310 / 718-920-4137
Categories Mesh Debug
Blood & Bone Marrow Cancers --- MYELOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- PERIPHERAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- NEUROMUSCULAR DISEASES
Blood & Bone Marrow Cancers --- CONGENITAL ABNORMALITIES
MeSH Terms
MYELOPROLIFERATIVE DISORDERS
PRIMARY MYELOFIBROSIS
HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
BONE MARROW DISEASES
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
NERVOUS SYSTEM MALFORMATIONS
NERVOUS SYSTEM DISEASES
HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM
NEURODEGENERATIVE DISEASES
POLYNEUROPATHIES
PERIPHERAL NERVOUS SYSTEM DISEASES
NEUROMUSCULAR DISEASES
CONGENITAL ABNORMALITIES
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
GENETIC DISEASES, INBORN
PARSACLISIB
RUXOLITINIB