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

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ClinicalTrials.gov Identifier: NCT03144687
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

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 subjects with myelofibrosis.

Condition or disease Intervention/treatment Phase
MPN (Myeloproliferative Neoplasms) Drug: Itacitinib Drug: Ruxolitinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 31, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Cohort A
Itacitinib plus ruxolitinib
Drug: Itacitinib
Itacitinib self-administered orally once daily at the protocol-defined dose.
Other Name: INCB039110

Drug: Ruxolitinib
Ruxolitinib self-administered orally at the stable dose of < 20 mg daily established before entering the study.
Other Names:
  • INCB018424
  • Jakafi
  • Jakavi

Experimental: Cohort B
Itacitinib alone
Drug: Itacitinib
Itacitinib self-administered orally once daily at the protocol-defined dose.
Other Name: INCB039110




Primary Outcome Measures :
  1. Change in spleen volume reduction [ Time Frame: Baseline through Week 24 ]
    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.

  2. Percentage change in spleen volume reduction [ Time Frame: Baseline through Week 24 ]
    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 :
  1. 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. ]
    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.

  2. 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 ]
    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.

  3. Change in spleen volume reduction [ Time Frame: Baseline through Week 12 ]
    Measured by MRI (CT scan in subjects who are not candidates for MRI or when MRI is not readily available).

  4. Percentage change in spleen volume reduction [ Time Frame: Baseline through Week 12 ]
    Measured by MRI (CT scan in subjects who are not candidates for MRI or when MRI is not readily available).

  5. Change in spleen length reduction [ Time Frame: Baseline through Week 12 and Week 24 ]
    Measured by palpation (in centimeters using a soft ruler).

  6. Percentage change in spleen length reduction [ Time Frame: Baseline through Week 12 and Week 24 ]
    Measured by palpation (in centimeters using a soft ruler).

  7. Change in Total Symptom Score [ Time Frame: Baseline through Week 12 and Week 24 ]
    Measured by the Myelofibrosis Symptom Assessment Form v2.0 and by the Myeloproliferative Neoplasm-Symptom Assessment Form.

  8. Percentage change in Total Symptom Score [ Time Frame: Baseline through Week 12 and Week 24 ]
    Measured by the Myelofibrosis Symptom Assessment Form v2.0 and by the Myeloproliferative Neoplasm-Symptom Assessment Form.

  9. 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. ]
    Subjects complete a 1-question assessment form of their myelofibrosis symptoms since the start of treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03144687


Contacts
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Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 globalmedinfo@incyte.com

  Show 31 Study Locations
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Fitzroy Dawkins, MD Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03144687     History of Changes
Other Study ID Numbers: INCB 39110-209
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
Myelofibrosis
Janus kinase (JAK) inhibitor
itacitinib
ruxolitinib
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases