Clinical trial NCT03320642: 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
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-10-25
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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).


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.

Primary outcomes:
measure: Proportion of participants with hematologic recovery when itacitinib is added to GVHD prophylaxis treatment
timeFrame: Day 28
Secondary outcomes:
measure: GVHD relapse-free survival rate
timeFrame: Days 100, 180 and 365
measure: Relapse-free survival
timeFrame: Up to 1 year
measure: Transplant-related mortality
timeFrame: Up to 1 year
measure: Median time to neutrophil and platelet engraftment
timeFrame: Up to Day 28
measure: Percentage of participants who achieve neutrophil and platelet engraftment
timeFrame: Up to Day 28
measure: Donor Chimerism
timeFrame: Up to Day 28
measure: Proportion of subjects who are diagnosed with Grade II-IV aGVHD, by each grade and by Grade III/IV
timeFrame: Days 100 and Days 180
measure: Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe)
timeFrame: Up to 1 year
measure: Infection rate
timeFrame: Up to 1 year
measure: Overall survival
timeFrame: Up to 1 year
measure: Participants with Grade 3-5 treatment-emergent adverse events (TEAEs)
timeFrame: Up to approximately 200 days
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion - University of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland - Greenebaum Cancer Center
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center, Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
city: Lille
country: France
facility: Chru de Lille Hopital Claude Huriez
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
city: Vandoeuvre-les-nancy
country: France
facility: Chu Vandoeuvre-Les-Nancy, Hopital Brabois
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo Di Monza
city: Pavia
country: Italy
facility: Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Incyte Corporation
name: Rodica Morariu-Zamfir, MD
role: STUDY_DIRECTOR
References: