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

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

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).

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.