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

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

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).

Study Overview

• Status: Terminated
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Itacitinib; Drug: Calcineurin inhibitor

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Days 100, 180 and 365
Relapse-free survival	Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.	Up to 1 year
Transplant-related mortality	Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.	Up to 1 year
Median time to neutrophil and platelet engraftment	Defined as the median time to achieve neutrophil and platelet engraftment.	Up to Day 28
Percentage of participants who achieve neutrophil and platelet engraftment	Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.	Up to Day 28
Donor Chimerism		Up to Day 28
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.	Days 100 and Days 180
Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe)	Measured to assess the incidence of cGVHD.	Up to 1 year
Infection rate	Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.	Up to 1 year
Overall survival	Defined as the interval between enrollment and death due to any cause.	Up to 1 year
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.	Up to approximately 200 days

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): February 17, 2022

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 25, 2017

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Hodgkin's lymphoma; myelodysplasia; mantle cell lymphoma; graft-versus-host disease; follicular; chronic myelogenous leukemia; Janus kinase inhibitor; Acute leukemia; marginal zone; chronic lymphocytic leukemia/small lymphocytic lymphoma; diffuse large B-cell
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Calcineurin Inhibitors
• Other Study ID Numbers: INCB 39110-119/GRAVITAS-119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No