A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

NCT02718300 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: INCB 50465-201Parsaclisib
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 39

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.

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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)

  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

Study Arms (4)

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.

Drug: Parsaclisib; Drug: Ruxolitinib

Part 2: Ruxolitinib + Parsaclisib

EXPERIMENTAL

Part 2 will compare 2 doses of parsaclisib .

Drug: Parsaclisib; Drug: Ruxolitinib

Part 3: Ruxolitinib + Parsaclisib

EXPERIMENTAL

Part 3 will compare 2 different long term dosing strategies.

Drug: Ruxolitinib; Drug: Parsaclisib

Part 4: Ruxolitinib + Parsaclisib

EXPERIMENTAL

Part 4 will compare 2 different daily dosing strategies.

Drug: Ruxolitinib; Drug: Parsaclisib

Interventions

Parsaclisib DRUG

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.

Also known as: INCB050465

Part 1: Ruxolitinib + Parsaclisib

Ruxolitinib DRUG

The dose of ruxolitinib will be that which the subjects had been taking for at least 8 weeks before the first dose of parsaclisib.

Also known as: Jakafi®

Part 1: Ruxolitinib + Parsaclisib; Part 2: Ruxolitinib + Parsaclisib; Part 3: Ruxolitinib + Parsaclisib; Part 4: Ruxolitinib + Parsaclisib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (39)

Birmingham Hematology & Oncolgy Associates Llc

Birmingham, Alabama, 35223, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Alta Bates Medical Center

Berkeley, California, 94704, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

California Cancer Associates For Research and Excellence

Fresno, California, 93720, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

Pcr Oncology

Pismo Beach, California, 93449, United States

Location

California Cancer Assoc. for Research and Excellence

San Marcos, California, 92069, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Shands Hospital

Gainesville, Florida, 32610, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, 46237, United States

Location

McFarland Clinic

Ames, Iowa, 50010, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Saint Agnes Hospital

Baltimore, Maryland, 21229, United States

Location

Cancer Center For Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63130, United States

Location

Summit Medical Group

Florham Park, New Jersey, 07932, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45230, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Rush University Medical Center

Nashville, Tennessee, 37203, United States

Location

Baylor Scott and White Research Institute

Dallas, Texas, 75246, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78217, United States

Location

Renovatio Clinical Consultants Llc

The Woodlands, Texas, 77380, United States

Location

Va Salt Lake City Health Care System

Salt Lake City, Utah, 84112, United States

Location

Vista Oncology Inc Ps

Olympia, Washington, 98506, United States

Location

Related Publications (1)

• 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.

  PMID: 38290135 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders; Primary Myelofibrosis; Hereditary Sensory and Autonomic Neuropathies

Interventions

parsaclisib; ruxolitinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Albert Assad, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: March 24, 2016
• Study Start: February 8, 2017
• Primary Completion: January 28, 2021
• Study Completion: April 29, 2022
• Last Updated: May 1, 2024
• Results First Posted: May 1, 2024

Record last verified: 2024-04

Locations

US (39)