Clinical trial NCT03144687: A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Participants With Myelofibrosis
Official title: An Open-Label Phase 2 Study of Itacitinib (INCB039110) in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Subjects With Myelofibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MPN (Myeloproliferative Neoplasms)
Keywords: Myelofibrosis
Janus kinase (JAK) inhibitor
itacitinib
ruxolitinib
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-05-09
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Spleen Volume at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
measure: Percentage Change in Spleen Volume at Week 24 Compared to Baseline
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: up to approximately 40 months (3.3 years)
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
timeFrame: up to approximately 40 months (3.3 years)
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: up to approximately 40 months (3.3 years)
measure: Change From Baseline Through Week 12 in SVR as Measured by MRI (or CT Scan in Applicable Participants)
timeFrame: Baseline through Week 12
measure: Percentage Change From Baseline Through Week 12 in SVR as Measured by MRI (or CT Scan in Applicable Participants)
timeFrame: Baseline through Week 12
measure: Change From Baseline Through Week 12 and Week 24 on Spleen Length as Measured by Palpation
timeFrame: Baseline through Weeks 12 and 24
measure: Percentage Change From Baseline Through Week 12 and Week 24 on Spleen Length as Measured by Palpation
timeFrame: Baseline through Weeks 12 and 24
measure: Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 Symptom Diary
timeFrame: Baseline through Weeks 12 and 24
measure: Percentage Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the MFSAF v2.0 Symptom Diary
timeFrame: Baseline through Weeks 12 and 24
measure: Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF)
timeFrame: Baseline through Week 12 and Week 24
measure: Percentage Change From Baseline Through Week 12 and Week 24 in Total Symptom Score as Measured by the MPN-SAF
timeFrame: Baseline through Week 12 and Week 24
measure: Patient Global Impression of Change (PGIC) Score at Each Visit
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 168
measure: Number of Participants With Responses According to the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Consensus Criteria for Treatment Response
timeFrame: up to approximately 40 months (3.3 years)
measure: Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for Itacitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) for Ruxolitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Apparent Oral Dose Clearance (CL/F) of Itacitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Apparent Oral Dose Clearance (CL/F) of Ruxolitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Maximum Observed Plasma Concentration (Cmax) of Itacitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Time to Maximum Concentration (Tmax) of Itacitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Time to Maximum Concentration (Tmax) of Ruxolitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Concentration at the End of the Dosing Interval (Ctau) of Itacitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose on Week 2 and Week 4
measure: Concentration at the End of the Dosing Interval (Ctau) of Ruxolitinib
timeFrame: 0 (pre-dose), 1, 2, 5 and 8 hours post-dose Week 2 and Week 4
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion - University Of Colorado
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Center
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialist
state: Nebraska
city: Albuquerque
country: United States
facility: University Of New Mexico Cancer Center
state: New Mexico
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute
state: Oregon
city: Broomall
country: United States
facility: Consultants in Medical Oncology and Hematology, PC
state: Pennsylvania
city: Round Rock
country: United States
facility: Texas Oncology - Round Rock Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH, Servicestelle für Studien
city: Salzburg
country: Austria
facility: Paracelsus Medical University Salzburg
city: Wien
country: Austria
facility: Hanusch Hospital
city: Amsterdam
country: Netherlands
facility: VU Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: UMC Utrecht Department of Hematology
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir
role: STUDY_DIRECTOR
References: