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TerminatedNCT03320642Updated Oct 21, 2025

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

A Phase 1 interventional study of Itacitinib and Calcineurin inhibitor in Hematologic Malignancies, sponsored by Incyte Corporation. Terminated at 17 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-21.

Sponsored by Incyte Corporation · Phase 1, Interventional, and Prevention

Why this study was terminated
Study terminated by sponsor
Phase
Phase 1
Study type
Interventional
Enrollment
84
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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).

02

Conditions studied

  • Hematologic Malignancies

Keywords

  • 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
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
84 participants (actual)

Study arms

  • Experimental
    Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions

    Itacitinib in combination with a CNI-based intervention.

    Drug: Itacitinib · Drug: Calcineurin inhibitor

Interventions

  • DrugItacitinib

    Itacitinib administered orally once daily at the protocol-defined dose.

    Also known as: INCB039110

  • DrugCalcineurin 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.

05

What researchers measure

Primary outcomes

  1. Proportion of participants with hematologic recovery when itacitinib is added to GVHD prophylaxis treatment

    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).

    Time frame: Day 28

Secondary outcomes

  1. GVHD relapse-free survival rate

    Defined as the proportion of subjects who do not experience Grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic therapy, malignancy relapse or progression, or death due to any cause.

    Time frame: Days 100, 180 and 365

  2. Relapse-free survival

    Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.

    Time frame: Up to 1 year

  3. Transplant-related mortality

    Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.

    Time frame: Up to 1 year

  4. Median time to neutrophil and platelet engraftment

    Defined as the median time to achieve neutrophil and platelet engraftment.

    Time frame: Up to Day 28

  5. Percentage of participants who achieve neutrophil and platelet engraftment

    Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.

    Time frame: Up to Day 28

  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

    Measured to assess the incidence of aGVHD.

    Time frame: Days 100 and Days 180

  8. Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe)

    Measured to assess the incidence of cGVHD.

    Time frame: Up to 1 year

  9. Infection rate

    Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.

    Time frame: Up to 1 year

  10. Overall survival

    Defined as the interval between enrollment and death due to any cause.

    Time frame: Up to 1 year

  11. Participants with Grade 3-5 treatment-emergent adverse events (TEAEs)

    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.

    Time frame: Up to approximately 200 days

06

Study locations

17 sites
  • Anschutz Cancer Pavilion - University of Colorado
    Aurora, Colorado 80045, United States
  • Winship Cancer Institute of Emory University
    Atlanta, Georgia 30322, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • University of Maryland - Greenebaum Cancer Center
    Baltimore, Maryland 21201, United States
  • Washington University School of Medicine
    St Louis, Missouri 63110, United States
  • John Theurer Cancer Center, Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
  • The Ohio State University
    Columbus, Ohio 43210, United States
  • Froedtert Hospital and the Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • Chru de Lille Hopital Claude Huriez
    Lille, 59037, France
  • Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
    Nantes, 44093, France
  • Chu Vandoeuvre-Les-Nancy, Hopital Brabois
    Vandœuvre-lès-Nancy, 54500, France
  • Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)
    Bergamo, 24127, Italy
  • Azienda Ospedaliera San Gerardo Di Monza
    Monza, 20900, Italy
  • Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
    Pavia, 27100, Italy
  • Hospital Puerta de Hierro
    Majadahonda, 28222, Spain
  • Hospital Clinico Universitario de Valencia
    Valencia, 46010, Spain
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03320642
Lead sponsor
Incyte Corporation
Responsible party
Sponsor
First posted
Oct 25, 2017
Start date
Feb 27, 2018
Primary completion
Feb 25, 2021
Completion
Feb 17, 2022
Last update
Oct 21, 2025

Study contacts

Rodica Morariu-Zamfir, MD
study director · Incyte Corporation

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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