Clinical Trials /

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

NCT03144687

Description:

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

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Itacitinib in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Subjects 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

Clinical Trial IDs

  • ORG STUDY ID: INCB 39110-209
  • NCT ID: NCT03144687

Conditions

  • MPN (Myeloproliferative Neoplasms)

Interventions

DrugSynonymsArms
ItacitinibINCB039110Cohort A
RuxolitinibINCB018424, Jakafi, JakaviCohort A

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalItacitinib plus ruxolitinib
  • Itacitinib
  • Ruxolitinib
Cohort BExperimentalItacitinib alone
  • Itacitinib

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 subjects

          -  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 ≥ 5 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 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 DNA and HCV RNA must be undetectable. Subjects cannot be positive
             for hepatitis B surface antigen or anti-hepatitis B core antibodies. Subjects 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. Subjects
             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
             subjects treated in Cohort A only).

          -  Inadequate recovery from toxicity and/or complications from a major surgery before
             starting therapy.

          -  Currently breastfeeding or pregnant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in spleen volume reduction
Time Frame:Baseline through Week 24
Safety Issue:
Description:Measured by magnetic resonance imaging (MRI); computed tomography (CT) scan in subjects who are not candidates for MRI or when MRI is not readily available.

Secondary Outcome Measures

Measure:Safety and tolerability of itacitinib alone through assessment of frequency, severity, and duration of adverse events (AEs)
Time Frame:Baseline through 30-35 days after last dose of itacitinib, up to 8 months per subject.
Safety Issue:
Description:An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent.
Measure:Safety and tolerability of itacitinib in combination with ruxolitinib through assessment of frequency, severity, and duration of AEs
Time Frame:Baseline through 30-35 days after last dose of itacitinib, up to 8 months per subject
Safety Issue:
Description:An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent.
Measure:Change in spleen volume reduction
Time Frame:Baseline through Week 12
Safety Issue:
Description:Measured by MRI (CT scan in subjects who are not candidates for MRI or when MRI is not readily available).
Measure:Percentage change in spleen volume reduction
Time Frame:Baseline through Week 12
Safety Issue:
Description:Measured by MRI (CT scan in subjects who are not candidates for MRI or when MRI is not readily available).
Measure:Change in spleen length reduction
Time Frame:Baseline through Week 12 and Week 24
Safety Issue:
Description:Measured by palpation (in centimeters using a soft ruler).
Measure:Percentage change in spleen length reduction
Time Frame:Baseline through Week 12 and Week 24
Safety Issue:
Description:Measured by palpation (in centimeters using a soft ruler).
Measure:Change in Total Symptom Score
Time Frame:Baseline through Week 12 and Week 24
Safety Issue:
Description:Measured by the Myelofibrosis Symptom Assessment Form v2.0 and by the Myeloproliferative Neoplasm-Symptom Assessment Form.
Measure:Percentage change in Total Symptom Score
Time Frame:Baseline through Week 12 and Week 24
Safety Issue:
Description:Measured by the Myelofibrosis Symptom Assessment Form v2.0 and by the Myeloproliferative Neoplasm-Symptom Assessment Form.
Measure:Change in Patient Global Impression of Change (PGIC) score
Time Frame:Protocol-defined timepoints from Week 4 through end of treatment, up to approximately 7 months per subject.
Safety Issue:
Description:Subjects complete a 1-question assessment form of their myelofibrosis symptoms since the start of treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

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

Last Updated

September 23, 2019