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

NCT ID: NCT02718300

Last Updated: 2024-05-01

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-08

Study Completion Date

2022-04-29

Brief Summary

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The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.

Detailed Description

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Conditions

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MPN (Myeloproliferative Neoplasms)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type 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.

Ruxolitinib

Intervention Type 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.

Part 2: Ruxolitinib + Parsaclisib

Part 2 will compare 2 doses of parsaclisib .

Group Type EXPERIMENTAL

Parsaclisib

Intervention Type DRUG

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.

Ruxolitinib

Intervention Type 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.

Part 3: Ruxolitinib + Parsaclisib

Part 3 will compare 2 different long term dosing strategies.

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type 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.

Parsaclisib

Intervention Type DRUG

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.

Part 4: Ruxolitinib + Parsaclisib

Part 4 will compare 2 different daily dosing strategies.

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type 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.

Parsaclisib

Intervention Type DRUG

2 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.

Interventions

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Parsaclisib

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.

Intervention Type DRUG

Parsaclisib

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.

Intervention Type DRUG

Ruxolitinib

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

Intervention Type DRUG

Parsaclisib

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.

Intervention Type DRUG

Parsaclisib

2 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.

Intervention Type DRUG

Other Intervention Names

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INCB050465 INCB050465 Jakafi® INCB050465 INCB050465

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Albert Assad, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Birmingham Hematology & Oncolgy Associates Llc

Birmingham, Alabama, United States

Site Status

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

Alta Bates Medical Center

Berkeley, California, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

California Cancer Associates For Research and Excellence

Fresno, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

UCLA School of Medicine

Los Angeles, California, United States

Site Status

Pcr Oncology

Pismo Beach, California, United States

Site Status

California Cancer Assoc. for Research and Excellence

San Marcos, California, United States

Site Status

Georgetown University Hospital

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

Site Status

Shands Hospital

Gainesville, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Indiana Blood and Marrow Transplantation

Indianapolis, Indiana, United States

Site Status

McFarland Clinic

Ames, Iowa, United States

Site Status

University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Saint Agnes Hospital

Baltimore, Maryland, United States

Site Status

Cancer Center For Blood Disorders

Bethesda, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Summit Medical Group

Florham Park, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Rush University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor Scott and White Research Institute

Dallas, Texas, United States

Site Status

Md Anderson Cancer Center

Houston, Texas, United States

Site Status

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Site Status

Renovatio Clinical Consultants Llc

The Woodlands, Texas, United States

Site Status

Va Salt Lake City Health Care System

Salt Lake City, Utah, United States

Site Status

Vista Oncology Inc Ps

Olympia, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 38290135 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Parsaclisib

Identifier Type: OTHER

Identifier Source: secondary_id

INCB 50465-201

Identifier Type: -

Identifier Source: org_study_id

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