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GRAVITAS-119: Itacitinib in Combination With Calcineurin Inhibitor-Based Interventions for the Prophylaxis of Graft-Versus Host Disease

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ClinicalTrials.gov Identifier: NCT03320642
Recruitment Status : Recruiting
First Posted : October 25, 2017
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study is to assess the impact and safety of itacitinib in combination with calcineurin inhibitor (CNI)-based interventions for the prophylaxis of graft-versus-host-disease (GVHD).

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Drug: Itacitinib Drug: Calcineurin inhibitor Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: GRAVITAS-119: A Single-Arm, Open-Label, Phase 1 Study of Itacitinib in Combination With Calcineurin Inhibitor-Based Interventions for the Prophylaxis of Graft-Versus Host Disease
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions
Itacitinib in combination with a CNI-based intervention.
Drug: Itacitinib
Itacitinib administered orally once daily at the protocol-defined dose.
Other Name: INCB039110

Drug: Calcineurin inhibitor
The CNI-based prophylaxis regimen will be identified by the investigator before the subject's enrollment and will consist of the combination of tacrolimus/methotrexate, cyclosporine A/mycophenolate mofetil or tacrolimus plus post-treatment cyclophosphamide. Antithymocyte globulin may be included at the treating investigator's discretion with the tacrolimus/methotrexate or cyclosporine A/mycophenolate mofetil combinations.




Primary Outcome Measures :
  1. Proportion of participants with hematologic recovery when itacitinib is added to GVHD prophylaxis treatment [ Time Frame: Day 28 ]
    Hematologic recovery defined as demonstrating both neutrophil recovery (ANC ≥ 500/mm^3 for 3 consecutive measurements) and platelet recovery (platelet count ≥ 20,000/mm^3 with no requirement for platelet transfusion in the preceding 3 days).


Secondary Outcome Measures :
  1. GVHD relapse-free survival rate [ Time Frame: Days 100, 180 and 365 ]
    Defined as the proportion of subjects who do not experience Grade II-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic therapy, malignancy relapse or progression, or death due to any cause.

  2. Relapse-free survival [ Time Frame: Up to 1 year ]
    Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.

  3. Transplant-related mortality [ Time Frame: Up to 1 year ]
    Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.

  4. Median time to neutrophil and platelet engraftment [ Time Frame: Up to Day 28 ]
    Defined as the median time to achieve engraftment and hematologic recovery.

  5. Percentage of participants who achieve neutrophil and platelet engraftment [ Time Frame: Up to Day 28 ]
    Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.

  6. Donor Chimerism [ Time Frame: Up to Day 28 ]
  7. Proportion of subjects who are diagnosed with Grade II-IV aGVHD, by each grade and by Grade III/IV [ Time Frame: Up to Day 180 ]
    Measured to assess the incidence of aGVHD.

  8. Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe) [ Time Frame: Up to 1 year ]
    Measured to assess the incidence of cGVHD.

  9. Infection rate [ Time Frame: Up to Day 180 ]
    Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.

  10. Overall survival [ Time Frame: Up to 1 year ]
    Defined as the interval between enrollment and death due to any cause.

  11. Participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to approximately 200 days ]
    TEAE is defined as either an adverse event (AE) reported for the first time or worsening of a pre-existing condition after the first dose of study treatment.



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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:

  • Subjects with acute leukemia, chronic myelogenous leukemia, or myelodysplasia with no circulating blasts and < 5% blasts in the bone marrow.
  • Subjects with non-Hodgkin lymphoma, including but not limited to chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular, marginal zone, diffuse large B cell, or mantle cell lymphoma must have chemosensitive disease at time of transplant. Subjects with Hodgkin lymphoma with chemosensitive disease at the time of transplant.
  • Must be candidates for reduced-intensity conditioning regimens.
  • Must be candidates for peripheral blood stem cell transplants.
  • Karnofsky Performance Status score ≥ 70% or Eastern Cooperative Oncology Group Performance Status score of 0 to 2.
  • Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min measured or calculated by Cockcroft-Gault equation.
  • Be willing to avoid pregnancy or fathering children.

Exclusion Criteria:

  • Has previously received an allogenic hematopoietic stem cell transplant.
  • Presence of an active uncontrolled infection.
  • Known HIV infection.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation.
  • Prior malignancies.
  • Severe organ dysfunction.
  • Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment.
  • Currently breastfeeding.
  • Known allergies, hypersensitivity, or intolerance to any of the study medications.
  • Receipt of live (including attenuated) vaccines during the study, or anticipation of need for such a vaccine during the study.
  • History of primary idiopathic myelofibrosis or any severe marrow fibrosis that would prolong neutrophil engraftment to > 28 days after transplant.
  • Post-transplant maintenance therapy for the hematologic malignancy or plans to initiate maintenance therapy during study treatment.

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): NCT03320642


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 25 Study Locations
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Rodica Morariu-Zamfir, MD Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03320642     History of Changes
Other Study ID Numbers: INCB 39110-119/GRAVITAS-119
First Posted: October 25, 2017    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
Acute leukemia
chronic myelogenous leukemia
myelodysplasia
chronic lymphocytic leukemia/small lymphocytic lymphoma
follicular
marginal zone
diffuse large B-cell
Hodgkin's lymphoma
mantle cell lymphoma
Janus kinase inhibitor
graft-versus-host disease
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action