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

Sponsor

Incyte Corporation (Industry)

Overall Status

Terminated

CT.gov ID

NCT03320642

Collaborator

(none)

Enrollment

Locations

Arm

47.7

Actual Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Drug: Itacitinib Drug: Calcineurin inhibitor	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Feb 27, 2018

Actual Primary Completion Date :

Feb 25, 2021

Actual Study Completion Date :

Feb 17, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.
Relapse-free survival [Up to 1 year]
Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.
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.
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.
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 [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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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