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

Hematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03320642
• Other study ID #: INCB 39110-119/GRAVITAS-119
• Status: Terminated
• Phase: Phase 1
• Start date: February 27, 2018
• Est. completion date: February 17, 2022

Study information

• Verified date: April 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 84
• Est. completion date: February 17, 2022
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Graft vs Host Disease
• Hematologic Malignancies
• Hematologic Neoplasms

Intervention

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

Locations

Country	Name	City	State
France	Chru de Lille Hopital Claude Huriez	Lille
France	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes
France	Chu Vandoeuvre-Les-Nancy, Hopital Brabois	Vandoeuvre-les-nancy
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii (Presidio Papa Giovanni Xxiii)	Bergamo
Italy	Azienda Ospedaliera San Gerardo Di Monza	Monza
Italy	Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo	Pavia
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Anschutz Cancer Pavilion - University of Colorado	Aurora	Colorado
United States	University of Maryland - Greenebaum Cancer Center	Baltimore	Maryland
United States	The Ohio State University	Columbus	Ohio
United States	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	Loyola University Medical Center	Maywood	Illinois
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Relapse-free survival	Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.	Up to 1 year
Secondary	Transplant-related mortality	Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.	Up to 1 year
Secondary	Median time to neutrophil and platelet engraftment	Defined as the median time to achieve neutrophil and platelet engraftment.	Up to Day 28
Secondary	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
Secondary	Donor Chimerism		Up to Day 28
Secondary	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
Secondary	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
Secondary	Infection rate	Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.	Up to 1 year
Secondary	Overall survival	Defined as the interval between enrollment and death due to any cause.	Up to 1 year
Secondary	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