MPN (Myeloproliferative Neoplasms)Phase 2NCT02718300
A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
A Phase 2 study testing Parsaclisib and Ruxolitinib in people with MPN (Myeloproliferative Neoplasms), run by Incyte Corporation at 39 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MPN (Myeloproliferative Neoplasms)
- What is being tested?
- Parsaclisib and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 39 sitesUnited States
- Study dates
- 8 Feb 2017to 29 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
39 sites in 1 country.
39 sites in 1 country
United States39 sites
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, 87106
McFarland Clinic
Ames, Iowa, 50010
Emory University
Atlanta, Georgia, 30322
Saint Agnes Hospital
Baltimore, Maryland, 21229
Alta Bates Medical Center
Berkeley, California, 94704
Cancer Center For Blood Disorders
Bethesda, Maryland, 20817
Birmingham Hematology & Oncolgy Associates Llc
Birmingham, Alabama, 35223
Massachusetts General Hospital
Boston, Massachusetts, 02114
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Chicago Medical Center
Chicago, Illinois, 60637
Oncology Hematology Care, Inc.
Cincinnati, Ohio, 45230
Cleveland Clinic
Cleveland, Ohio, 44195
Baylor Scott and White Research Institute
Dallas, Texas, 75246
City of Hope National Medical Center
Duarte, California, 91010
Summit Medical Group
Florham Park, New Jersey, 07932
California Cancer Associates For Research and Excellence
Fresno, California, 93720
Shands Hospital
Gainesville, Florida, 32610
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Md Anderson Cancer Center
Houston, Texas, 77030
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, 46237
University of Southern California
Los Angeles, California, 90033
UCLA School of Medicine
Los Angeles, California, 90095
Norton Cancer Institute
Louisville, Kentucky, 40202
Rush University Medical Center
Nashville, Tennessee, 37203
Mount Sinai School of Medicine
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Vista Oncology Inc Ps
Olympia, Washington, 98506
Pcr Oncology
Pismo Beach, California, 93449
Oregon Health & Science University
Portland, Oregon, 97239
Va Salt Lake City Health Care System
Salt Lake City, Utah, 84112
Cancer Care Centers of South Texas
San Antonio, Texas, 78217
California Cancer Assoc. for Research and Excellence
San Marcos, California, 92069
Mayo Clinic Arizona
Scottsdale, Arizona, 85259
Washington University School of Medicine
St Louis, Missouri, 63130
Montefiore Medical Center
The Bronx, New York, 10467
Renovatio Clinical Consultants Llc
The Woodlands, Texas, 77380
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
University of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.
- Conditions
- MPN (Myeloproliferative Neoplasms)
- Being tested
- Parsaclisib, Ruxolitinib
- 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
- Medical subject headings
- Myeloproliferative Disorders, Primary Myelofibrosis, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParsaclisibDrug
Also called INCB050465
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.
ParsaclisibDrug
Also called INCB050465
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.
RuxolitinibDrug
Also called Jakafi®
The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.
ParsaclisibDrug
Also called INCB050465
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.
ParsaclisibDrug
Also called INCB050465
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.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Ruxolitinib + Parsaclisib | Experimental | Initial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria. Receives: Drug: Parsaclisib; Drug: Ruxolitinib |
| Part 2: Ruxolitinib + Parsaclisib | Experimental | Part 2 will compare 2 doses of parsaclisib . Receives: Drug: Parsaclisib; Drug: Ruxolitinib |
| Part 3: Ruxolitinib + Parsaclisib | Experimental | Part 3 will compare 2 different long term dosing strategies. Receives: Drug: Ruxolitinib; Drug: Parsaclisib |
| Part 4: Ruxolitinib + Parsaclisib | Experimental | Part 4 will compare 2 different daily dosing strategies. Receives: Drug: Ruxolitinib; Drug: Parsaclisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities (DLTs)
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.
Measured: up to Day 28
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)
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 12
Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants)
Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100.
Measured: Baseline; Week 12
Secondary outcomes (29)
Change From Baseline in Spleen Volume Through Week 24 of the Initial Study Period as Measured by MRI (or CT Scan in Applicable Participants)
Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Measured: Baseline; Week 24
Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants )
Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] / Baseline value) x 100.
Measured: 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
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.
Measured: Baseline; Week 12
Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary
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.
Measured: Baseline; Week 12
Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
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.
Measured: Baseline; Week 24
Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
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.
Measured: Baseline; Week 24
Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
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.
Measured: Baseline; Week 12
Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF
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.
Measured: Baseline; Week 12
Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
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.
Measured: Baseline; Week 24
Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
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.
Measured: 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)
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."
Measured: Baseline; up to 1494 days (EOT)
Mean PGIC Score at Week 12, Week 24, and the EOT
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."
Measured: 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
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.
Measured: Week 12 and every 12 weeks thereafter (up to 1494 days [EOT])
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
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.
Measured: up to approximately 4 years
Number of Participants With Any TEAE During the Transition Period
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.
Measured: up to approximately 4 years
Cmax of Parsaclisib
Cmax was defined as the maximum observed plasma concentration.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Tmax of Parsaclisib
tmax was defined as the time to the maximum concentration.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Cmin of Parsaclisib
Cmin was defined as the minimum observed plasma concentration.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-4h of Parsaclisib
AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-t of Parsaclisib
AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Clast of Parsaclisib
Clast was defined as the last quantifiable concentration.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Tlast of Parsaclisib
tlast was defined as the time of the last quantifiable concentration.
Measured: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Cmax of Ruxolitinib
Cmax was defined as the maximum observed plasma concentration.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Tmax of Ruxolitinib
tmax was defined as the time to the maximum concentration.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Cmin of Ruxolitinib
Cmin was defined as the minimum observed plasma concentration.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-4h of Ruxolitinib
AUC0-4h was defined as the area under the plasma concentration-time curve from time = 0 to 4 hours post-dose.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-t of Ruxolitinib
AUC0-t was defined as the area under the plasma concentration-time curve from time =0 to the last measurable concentration at time = t.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Clast of Ruxolitinib
Clast was defined as the last quantifiable concentration.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Tlast of Ruxolitinib
tlast was defined as the time of the last quantifiable concentration.
Measured: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study start8 Feb 2017
- Primary completion28 Jan 2021
- Study completion29 Apr 2022
Why it stopped: A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MPN (Myeloproliferative Neoplasms)Studies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Albert Assad, MD, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02718300
- Sponsor's protocol ID
- INCB 50465-201
- Other IDs
- Parsaclisib
- Status last verified
- Apr 2024
- First submitted
- 21 Mar 2016
- Last updated
- 1 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
Yacoub A, Borate U, Rampal RK, Ali H, Wang ES, Gerds AT, Hobbs G, Kremyanskaya M, Winton E, O'Connell C, Goel S, Oh ST, Schiller G, McCloskey J, Palmer J, Holmes H, Hager S, Assad A, Erickson-Viitanen S, Zhou F, Daver N. Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results. Blood Adv. 2024 Mar 26;8(6):1515-1528. doi: 10.1182/bloodadvances.2023011620.
PubMed 38290135
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis
- ClinicalTrials.gov ID
- NCT02718300
- Acronym / sponsor ID
- INCB 50465-201
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 8 Feb 2017 (actual)
- Primary completion
- 28 Jan 2021 (actual)
- Study completion
- 29 Apr 2022 (actual)
- First posted
- 24 Mar 2016 (estimated)
- Results
- Posted 1 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: Ruxolitinib + Parsaclisib | Experimental | Drug: Parsaclisib, Drug: RuxolitinibInitial cohort dose of parsaclisib added to existing stable regimen of ruxolitinib, with subsequent cohort escalations based on protocol-specific criteria. |
| Part 2: Ruxolitinib + Parsaclisib | Experimental | Drug: Parsaclisib, Drug: RuxolitinibPart 2 will compare 2 doses of parsaclisib . |
| Part 3: Ruxolitinib + Parsaclisib | Experimental | Drug: Ruxolitinib, Drug: ParsaclisibPart 3 will compare 2 different long term dosing strategies. |
| Part 4: Ruxolitinib + Parsaclisib | Experimental | Drug: Ruxolitinib, Drug: ParsaclisibPart 4 will compare 2 different daily dosing strategies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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:
- Inadequate liver function at screening as demonstrated by the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParsaclisibAlso: INCB050465Up 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. | Drug | Part 1: Ruxolitinib + Parsaclisib |
| ParsaclisibAlso: INCB050465Two 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. | Drug | Part 2: Ruxolitinib + Parsaclisib |
| RuxolitinibAlso: Jakafi®The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib. | Drug | Part 1: Ruxolitinib + Parsaclisib, Part 2: Ruxolitinib + Parsaclisib, Part 3: Ruxolitinib + Parsaclisib, Part 4: Ruxolitinib + Parsaclisib |
| ParsaclisibAlso: INCB05046520 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. | Drug | Part 3: Ruxolitinib + Parsaclisib |
| ParsaclisibAlso: INCB0504652 dose strategies will be compared: 1. 5 mg parsaclisib beginning on Day 1 until end of treatment. 2. 20 mg oral QD dose of parsaclisib for 8 weeks; after 8 weeks patients will take 5 mg once daily. | Drug | Part 4: Ruxolitinib + Parsaclisib |
Primary outcome
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.
29 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)
Time frame: Baseline; Week 24
Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants )
Time frame: 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
Time frame: Baseline; Week 12
Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary
Time frame: Baseline; Week 12
Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
Time frame: Baseline; Week 24
Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary
Time frame: Baseline; Week 24
Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Time frame: Baseline; Week 12
Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF
Time frame: Baseline; Week 12
Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
Time frame: Baseline; Week 24
Percent Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF
Time frame: 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)
Time frame: Baseline; up to 1494 days (EOT)
Mean PGIC Score at Week 12, Week 24, and the EOT
Time frame: 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
Time frame: Week 12 and every 12 weeks thereafter (up to 1494 days [EOT])
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Time frame: up to approximately 4 years
Number of Participants With Any TEAE During the Transition Period
Time frame: up to approximately 4 years
Cmax of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Tmax of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Cmin of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-4h of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-t of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Clast of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Tlast of Parsaclisib
Time frame: Week 2 and Week 4: predose and 1, 2, and 4 hours post-dose
Cmax of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Tmax of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Cmin of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-4h of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
AUC0-t of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Clast of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Tlast of Ruxolitinib
Time frame: Day 1 and Week 4: predose and 1, 2, and 4 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38290135Yacoub A, Borate U, Rampal RK, Ali H, Wang ES, Gerds AT, Hobbs G, Kremyanskaya M, Winton E, O'Connell C, Goel S, Oh ST, Schiller G, McCloskey J, Palmer J, Holmes H, Hager S, Assad A, Erickson-Viitanen S, Zhou F, Daver N. Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results. Blood Adv. 2024 Mar 26;8(6):1515-1528. doi: 10.1182/bloodadvances.2023011620.
Related trials for MPN (Myeloproliferative Neoplasms)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingPhase 1
A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms
Polycythemia Vera (PV), Myelofibrosis (MF)
Not yet recruitingPhase 2
Oral Tetrahydrouridine-Decitabine in Patients With Advanced Myeloproliferative Neoplasms
Myelofibrosis, MPN - Accelerated or Blast Phase
RecruitingObservational study
Screening Study for KIT D816V Mutated Mast Cell Disease in Select Populations
Clonal Mast Cell Disease, KIT D816V Mutation
Not yet recruiting
WELL-MPN: A Digital Lifestyle App for Patients With MPNs
Myeloproliferative Neoplasms (MPNs)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Assad, MD study director
Incyte Corporation
39 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Parsaclisib and Ruxolitinib in people with MPN (Myeloproliferative Neoplasms), run by Incyte Corporation at 39 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: up to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02718300, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2024.