GRAVITAS-119: Itacitinib in Combination With Calcineurin Inhibitor-Based Interventions for the Prophylaxis of Graft-Versus Host Disease
- Conditions
- Hematologic Malignancies
- Interventions
- Drug: Calcineurin inhibitor
- Registration Number
- NCT03320642
- Lead Sponsor
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 84
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions Calcineurin inhibitor Itacitinib in combination with a CNI-based intervention. Itacitinib + Calcineurin Inhibitor (CNI) -Based Interventions Itacitinib Itacitinib in combination with a CNI-based intervention.
- Primary Outcome Measures
Name Time Method Proportion of participants with hematologic recovery when itacitinib is added to GVHD prophylaxis treatment 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
Name Time Method GVHD relapse-free survival rate Days 100, 180 and 365 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.
Transplant-related mortality Up to 1 year Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.
Median time to neutrophil and platelet engraftment Up to Day 28 Defined as the median time to achieve neutrophil and platelet engraftment.
Donor Chimerism Up to Day 28 Infection rate Up to 1 year Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.
Overall survival Up to 1 year Defined as the interval between enrollment and death due to any cause.
Relapse-free survival Up to 1 year Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.
Participants with Grade 3-5 treatment-emergent adverse events (TEAEs) 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.
Percentage of participants who achieve neutrophil and platelet engraftment Up to Day 28 Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.
Proportion of subjects who are diagnosed with Grade II-IV aGVHD, by each grade and by Grade III/IV Days 100 and Days 180 Measured to assess the incidence of aGVHD.
Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe) Up to 1 year Measured to assess the incidence of cGVHD.
Trial Locations
- Locations (17)
Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
🇮🇹Pavia, Italy
Chru de Lille Hopital Claude Huriez
🇫🇷Lille, France
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
University of Maryland - Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)
🇮🇹Bergamo, Italy
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
🇫🇷Nantes, France
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Azienda Ospedaliera San Gerardo Di Monza
🇮🇹Monza, Italy
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hospital Puerta de Hierro
🇪🇸Majadahonda, Spain
Chu Vandoeuvre-Les-Nancy, Hopital Brabois
🇫🇷Vandoeuvre-les-nancy, France
John Theurer Cancer Center, Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Anschutz Cancer Pavilion - University of Colorado
🇺🇸Aurora, Colorado, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States