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

NCT03144687 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: INCB 39110-2092017-005109-11
• Study Type: interventional
• Target: 23
• Locations: 3 countries
• Sites: 26

Brief Summary

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).

Conditions

MPN (Myeloproliferative Neoplasms)

Keywords

Myelofibrosis; Janus kinase (JAK) inhibitor; itacitinib; ruxolitinib

Outcome Measures

Primary Outcomes (2)

• Change in Spleen Volume at Week 24 Compared to Baseline

  Spleen volume was measured using magnetic resonance imaging (MRI) or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.

  Baseline and Week 24

• Percentage Change in Spleen Volume at Week 24 Compared to Baseline

  Spleen volume was measured using MRI or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.

  Baseline and Week 24

Secondary Outcomes (23)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  up to approximately 40 months (3.3 years)

• Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters

  up to approximately 40 months (3.3 years)

• Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

  up to approximately 40 months (3.3 years)

• Change From Baseline Through Week 12 in SVR as Measured by MRI (or CT Scan in Applicable Participants)

  Baseline through Week 12

• Percentage Change From Baseline Through Week 12 in SVR as Measured by MRI (or CT Scan in Applicable Participants)

  Baseline through Week 12

Study Arms (2)

Cohort A

EXPERIMENTAL

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.

Drug: Itacitinib; Drug: Ruxolitinib

Cohort B

EXPERIMENTAL

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.

Drug: Itacitinib

Interventions

Itacitinib DRUG

Itacitinib self-administered orally once daily .

Also known as: INCB039110

Cohort A; Cohort B

Ruxolitinib DRUG

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

Also known as: INCB018424, Jakafi, Jakavi

Cohort A

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (26)

Arizona Oncology Associates

Tempe, Arizona, 85284, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Anschutz Cancer Pavilion - University Of Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Center

Colorado Springs, Colorado, 80907, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Providence Cancer Center

Southfield, Michigan, 48075, United States

Location

Nebraska Cancer Specialist

Omaha, Nebraska, 68124, United States

Location

University Of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Willamette Valley Cancer Institute

Eugene, Oregon, 97401, United States

Location

Consultants in Medical Oncology and Hematology, PC

Broomall, Pennsylvania, 19008, United States

Location

Texas Oncology - Round Rock Cancer Center

Round Rock, Texas, 78681, United States

Location

Texas Oncology San Antonio

San Antonio, Texas, 78240, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Ordensklinikum Linz GmbH, Servicestelle für Studien

Linz, 4020, Austria

Location

Paracelsus Medical University Salzburg

Salzburg, A-5020, Austria

Location

Hanusch Hospital

Vienna, 1140, Austria

Location

VU Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6202, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 AA, Netherlands

Location

UMC Utrecht Department of Hematology

Utrecht, 3584, Netherlands

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Primary Myelofibrosis

Interventions

itacitinib; INCB039110; ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Peter Langmuir

  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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2017
• First Posted: May 9, 2017
• Study Start: January 26, 2018
• Primary Completion: March 14, 2020
• Study Completion: June 1, 2021
• Last Updated: June 16, 2022
• Results First Posted: July 2, 2021

Record last verified: 2022-05

Locations

NL (4); US (19); AU (3)