A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Participants With Myelofibrosis

NCT ID: NCT03144687

Last Updated: 2022-06-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-26

Study Completion Date

2021-06-01

Brief Summary

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The purpose of this study is to evaluate the efficacy and safety of itacitinib combined with low-dose ruxolitinib or itacitinib alone in participants with myelofibrosis (MF).

Detailed Description

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Conditions

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MPN (Myeloproliferative Neoplasms)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A

Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of the itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment are met.

Group Type EXPERIMENTAL

Itacitinib

Intervention Type DRUG

Itacitinib self-administered orally once daily .

Ruxolitinib

Intervention Type DRUG

Ruxolitinib self-administered orally at the stable dose of \< 20 mg daily established before entering the study.

Cohort B

Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment are met.

Group Type EXPERIMENTAL

Itacitinib

Intervention Type DRUG

Itacitinib self-administered orally once daily .

Interventions

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Itacitinib

Itacitinib self-administered orally once daily .

Intervention Type DRUG

Ruxolitinib

Ruxolitinib self-administered orally at the stable dose of \< 20 mg daily established before entering the study.

Intervention Type DRUG

Other Intervention Names

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INCB039110 INCB018424 Jakafi Jakavi

Eligibility Criteria

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Inclusion Criteria

Cohort A only

•Receiving ruxolitinib dose of less than 20 mg daily with no dose increase or no dose modification in the last 8 weeks before screening visit.

Cohort B only

•Must have had initial reduction in spleen on ruxolitinib treatment:

* Followed by documented evidence of progression in spleen length or volume OR
* Discontinued ruxolitinib for hematologic toxicities, after the initial reduction in spleen length or volume.

All participants

* Confirmed diagnosis of primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis according to revised World Health Organization 2016 criteria.
* Must have palpable spleen of greater than or equal to (≥) 5 centimeter (cm) below the left subcostal margin on physical examination at the screening visit.
* Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
* Screening bone marrow biopsy specimen available or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24.
* Life expectancy of at least 24 weeks.
* Willingness to avoid pregnancy or fathering children

Exclusion Criteria

* Lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
* Previous treatment with itacitinib or Janus kinase (JAK1) inhibitors (JAK1/JAK2 inhibitor ruxolitinib is permitted).
* Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
* Recent history of inadequate bone marrow reserve as demonstrated by protocol-defined criteria.
* Inadequate liver function at screening and baseline visits as demonstrated by protocol-defined criteria.
* Inadequate renal function at screening and baseline visits as demonstrated by protocol-defined criteria.
* Active bacterial, fungal, parasitic, or viral infection that requires therapy.
* Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation: HBV deoxyribonucleic acid (DNA) and HCV ribonucleic acid (RNA) must be undetectable. Participants cannot be positive for hepatitis B surface antigen or anti-hepatitis B core antibodies. Participants who have positive anti-HBs as the only evidence of prior exposure may participate in the study provided that there is both 1) no known history of HBV infection and 2) verified receipt of hepatitis B vaccine.
* Known human immunodeficiency virus infection.
* Clinically significant or uncontrolled cardiac disease.
* Active invasive malignancy over the previous 2 years except treated basal or squamous carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers. Participants with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery may be enrolled as long as they have a reasonable expectation to have been cured with the treatment modality received.
* Splenic irradiation within 6 months before receiving the first dose of itacitinib.
* Use of any prohibited concomitant medications.
* Active alcohol or drug addiction that would interfere with their ability to comply with the study requirements.
* Use of any potent/strong cytochrome P450 3A4 inhibitors within 14 days or 5 half-lives (whichever is longer) before the first dose of itacitinib or anticipated during the study.
* Use of concomitant treatment of fluconazole at a dose \> 200 mg (for ruxolitinib participants treated in Cohort A only).
* Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
* Currently breastfeeding or pregnant.
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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Peter Langmuir

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Arizona Oncology Associates

Tempe, Arizona, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

Anschutz Cancer Pavilion - University Of Colorado

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Center

Colorado Springs, Colorado, United States

Site Status

Rocky Mountain Cancer Center

Denver, Colorado, United States

Site Status

Norwalk Hospital

Norwalk, Connecticut, United States

Site Status

Parkview Research Center

Fort Wayne, Indiana, United States

Site Status

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status

Providence Cancer Center

Southfield, Michigan, United States

Site Status

Nebraska Cancer Specialist

Omaha, Nebraska, United States

Site Status

University Of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Willamette Valley Cancer Institute

Eugene, Oregon, United States

Site Status

Consultants in Medical Oncology and Hematology, PC

Broomall, Pennsylvania, United States

Site Status

Texas Oncology - Round Rock Cancer Center

Round Rock, Texas, United States

Site Status

Texas Oncology San Antonio

San Antonio, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Ordensklinikum Linz GmbH, Servicestelle für Studien

Linz, , Austria

Site Status

Paracelsus Medical University Salzburg

Salzburg, , Austria

Site Status

Hanusch Hospital

Vienna, , Austria

Site Status

VU Medical Center

Amsterdam, , Netherlands

Site Status

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

UMC Utrecht Department of Hematology

Utrecht, , Netherlands

Site Status

Countries

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United States Austria Netherlands

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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2017-005109-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 39110-209

Identifier Type: -

Identifier Source: org_study_id

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