Hematologic Malignancies
Conditions
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
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).
Interventions
DRUGItacitinib
Itacitinib administered orally once daily at the protocol-defined dose.
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.
Sponsors
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
| 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. |
| 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. |
Countries
France, Italy, Spain, United States
Outcome results
None listed