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

• ClinicalTrials.gov Identifier: NCT03320642
• Recruitment Status: Recruiting
• First Posted: October 25, 2017
• Last Update Posted: November 13, 2019
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

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 (Clinical Trial)
• Estimated Enrollment: 85 participants
• 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: January 31, 2018
• Estimated Primary Completion Date: July 2020
• Estimated Study Completion Date: July 2021

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 Name: 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 :

1. Proportion of participants with hematologic recovery when itacitinib is added to GVHD prophylaxis treatment [ Time Frame: 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 :

1. GVHD relapse-free survival rate [ Time Frame: Days 100, 180 and 365 ]
   Defined as the proportion of subjects who do not experience Grade II-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic therapy, malignancy relapse or progression, or death due to any cause.
2. Relapse-free survival [ Time Frame: Up to 1 year ]
   Defined as the interval between enrollment and malignancy relapse or progression, or death, whichever occurs first.
3. Transplant-related mortality [ Time Frame: Up to 1 year ]
   Defined as the proportion of subjects who die due to causes other than malignancy relapse or progression.
4. Median time to neutrophil and platelet engraftment [ Time Frame: Up to Day 28 ]
   Defined as the median time to achieve engraftment and hematologic recovery.
5. Percentage of participants who achieve neutrophil and platelet engraftment [ Time Frame: Up to Day 28 ]
   Defined as the median time to achieve engraftment and hematologic recovery at prespecified time points.
6. Donor Chimerism [ Time Frame: Up to Day 28 ]
7. Proportion of subjects who are diagnosed with Grade II-IV aGVHD, by each grade and by Grade III/IV [ Time Frame: Up to Day 180 ]
   Measured to assess the incidence of aGVHD.
8. Proportion of subjects who are diagnosed with cGVHD by grade (mild, moderate, or severe) [ Time Frame: Up to 1 year ]
   Measured to assess the incidence of cGVHD.
9. Infection rate [ Time Frame: Up to Day 180 ]
   Defined as the proportion of subjects who demonstrate an infection and/or cytomegalovirus reactivation.
10. Overall survival [ Time Frame: Up to 1 year ]
    Defined as the interval between enrollment and death due to any cause.
11. Participants with treatment-emergent adverse events (TEAEs) [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Incyte Corporation Call Center (US); 1.855.463.3463; medinfo@incyte.com

Contact: Incyte Corporation Call Center (ex-US); +800 00027423; globalmedinfo@incyte.com

  Show 25 Study Locations

Sponsors and Collaborators

Incyte Corporation

Investigators

• Study Director: Rodica Morariu-Zamfir, MD; Incyte Corporation

More Information

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03320642 History of Changes
• Other Study ID Numbers: INCB 39110-119/GRAVITAS-119
• First Posted: October 25, 2017
• Last Update Posted: November 13, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:

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

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action