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

NCT03320642 | Terminated Phase 1 FDA Drug

• 2 other identifiers: INCB 39110-119/GRAVITAS-1192017-002922-19
• Study Type: interventional
• Target: 84
• Locations: 4 countries
• Sites: 17

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).

Conditions

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

Outcome Measures

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).

  Day 28

Secondary Outcomes (11)

• GVHD relapse-free survival rate

  Days 100, 180 and 365

• Relapse-free survival

  Up to 1 year

• Transplant-related mortality

  Up to 1 year

• Median time to neutrophil and platelet engraftment

  Up to Day 28

• Percentage of participants who achieve neutrophil and platelet engraftment

  Up to Day 28

Study Arms (1)

Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions

EXPERIMENTAL

Itacitinib in combination with a CNI-based intervention.

Drug: Itacitinib; Drug: Calcineurin inhibitor

Interventions

Itacitinib DRUG

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

Also known as: INCB039110

Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions

Calcineurin inhibitor DRUG

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.

Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (17)

Anschutz Cancer Pavilion - University of Colorado

Aurora, Colorado, 80045, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Maryland - Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Chru de Lille Hopital Claude Huriez

Lille, 59037, France

Location

Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu

Nantes, 44093, France

Location

Chu Vandoeuvre-Les-Nancy, Hopital Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)

Bergamo, 24127, Italy

Location

Azienda Ospedaliera San Gerardo Di Monza

Monza, 20900, Italy

Location

Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo

Pavia, 27100, Italy

Location

Hospital Puerta de Hierro

Majadahonda, 28222, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anemia, Refractory, with Excess of Blasts; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Graft vs Host Disease

Interventions

itacitinib; INCB039110; Calcineurin Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Rodica Morariu-Zamfir, MD

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: October 25, 2017
• Study Start: February 27, 2018
• Primary Completion: February 25, 2021
• Study Completion: February 17, 2022
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (9); FR (3); IT (3)