Back to resultsGRAVITAS-119: Itacitinib in Combination With Calcineurin Inhibitor-Based Interventions for the Prophylaxis of Graft-Versus Host Disease
Primary Purpose
Hematologic Malignancies
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Itacitinib
Calcineurin inhibitor
Sponsored by
About this trial
This is an interventional prevention trial for Hematologic Malignancies focused on measuring 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
Eligibility 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.
Sites / Locations
- Anschutz Cancer Pavilion - University of Colorado
- Winship Cancer Institute of Emory University
- Loyola University Medical Center
- University of Maryland - Greenebaum Cancer Center
- Washington University School of Medicine
- John Theurer Cancer Center, Hackensack University Medical Center
- Memorial Sloan Kettering Cancer Center
- The Ohio State University
- Froedtert Hospital and the Medical College of Wisconsin
- Chru de Lille Hopital Claude Huriez
- Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
- Chu Vandoeuvre-Les-Nancy, Hopital Brabois
- Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)
- Azienda Ospedaliera San Gerardo Di Monza
- Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
- Hospital Puerta de Hierro
- Hospital Clinico Universitario de Valencia
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions
Arm Description
Itacitinib in combination with a CNI-based intervention.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
Relapse-free survival
Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.
Transplant-related mortality
Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.
Median time to neutrophil and platelet engraftment
Defined as the median time to achieve neutrophil and platelet engraftment.
Percentage of participants who achieve neutrophil and platelet engraftment
Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.
Donor Chimerism
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.
Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe)
Measured to assess the incidence of cGVHD.
Infection rate
Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.
Overall survival
Defined as the interval between enrollment and death due to any cause.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03320642
Brief Title
GRAVITAS-119: Itacitinib in Combination With Calcineurin Inhibitor-Based Interventions for the Prophylaxis of Graft-Versus Host Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Terminated
Why Stopped
Study terminated by sponsor
Study Start Date
February 27, 2018 (Actual)
Primary Completion Date
February 25, 2021 (Actual)
Study Completion Date
February 17, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
84 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions
Arm Type
Experimental
Arm Description
Itacitinib in combination with a CNI-based intervention.
Intervention Type
Drug
Intervention Name(s)
Itacitinib
Other Intervention Name(s)
INCB039110
Intervention Description
Itacitinib administered orally once daily at the protocol-defined dose.
Intervention Type
Drug
Intervention Name(s)
Calcineurin inhibitor
Intervention Description
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 Measure Information:
Title
Proportion of participants with hematologic recovery when itacitinib is added to GVHD prophylaxis treatment
Description
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 Outcome Measure Information:
Title
GVHD relapse-free survival rate
Description
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
Title
Relapse-free survival
Description
Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.
Time Frame
Up to 1 year
Title
Transplant-related mortality
Description
Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.
Time Frame
Up to 1 year
Title
Median time to neutrophil and platelet engraftment
Description
Defined as the median time to achieve neutrophil and platelet engraftment.
Time Frame
Up to Day 28
Title
Percentage of participants who achieve neutrophil and platelet engraftment
Description
Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.
Time Frame
Up to Day 28
Title
Donor Chimerism
Time Frame
Up to Day 28
Title
Proportion of subjects who are diagnosed with Grade II-IV aGVHD, by each grade and by Grade III/IV
Description
Measured to assess the incidence of aGVHD.
Time Frame
Days 100 and Days 180
Title
Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe)
Description
Measured to assess the incidence of cGVHD.
Time Frame
Up to 1 year
Title
Infection rate
Description
Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.
Time Frame
Up to 1 year
Title
Overall survival
Description
Defined as the interval between enrollment and death due to any cause.
Time Frame
Up to 1 year
Title
Participants with Grade 3-5 treatment-emergent adverse events (TEAEs)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rodica Morariu-Zamfir, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Anschutz Cancer Pavilion - University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
University of Maryland - Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
John Theurer Cancer Center, Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Froedtert Hospital and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Chru de Lille Hopital Claude Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Chu Vandoeuvre-Les-Nancy, Hopital Brabois
City
Vandoeuvre-les-nancy
ZIP/Postal Code
54500
Country
France
Facility Name
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Facility Name
Azienda Ospedaliera San Gerardo Di Monza
City
Monza
ZIP/Postal Code
20900
Country
Italy
Facility Name
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
GRAVITAS-119: Itacitinib in Combination With Calcineurin Inhibitor-Based Interventions for the Prophylaxis of Graft-Versus Host Disease
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