Purpose

The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria - Underwent allogeneic stem cell transplantation (allo-HCT) - Karnofsky Performance Status score ≥ 60%. - Evidence of myeloid and platelet engraftment. - Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.

Exclusion Criteria

  • Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD. - Has received any other systemic treatment for cGVHD, including extracorporeal photopheresis (ECP). - Prior treatment with a Janus kinase (JAK) inhibitor for acute GVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization. - cGVHD occurring after a nonscheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. - Evidence of relapsed primary malignancy.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
In Part 2 of the study, participants in the placebo group will be allowed to cross over to the experimental group after completion of the primary analysis.
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 : Dose determination of itacitinib
itacitinib administered in combination with corticosteroids.
  • Drug: Itacitinib
    In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.
    Other names:
    • INCB039110
  • Drug: Methylprednisolone
    Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
    Other names:
    • Medrol, Medrol Dosepak, Solu-Medrol
  • Drug: Prednisone
    Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
    Other names:
    • Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS
Experimental
Part 1 : Dose expansion of itacitinib
itacitinib administered in combination with corticosteroids or corticosteroids alone.
  • Drug: Itacitinib
    In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.
    Other names:
    • INCB039110
  • Drug: Placebo
    In Part 2, participants will receive matching placebo.
  • Drug: Methylprednisolone
    Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
    Other names:
    • Medrol, Medrol Dosepak, Solu-Medrol
  • Drug: Prednisone
    Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
    Other names:
    • Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS
Placebo Comparator
Part 2 : itacitinib recommended dose from part 1
itacitinib or placebo administered in combination with corticosteroids
  • Drug: Itacitinib
    In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion.
    Other names:
    • INCB039110
  • Drug: Methylprednisolone
    Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
    Other names:
    • Medrol, Medrol Dosepak, Solu-Medrol
  • Drug: Prednisone
    Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
    Other names:
    • Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS

Recruiting Locations

More Details

NCT ID
NCT03584516
Status
Terminated
Sponsor
Incyte Corporation

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.