Study of Itacitinib in Combination With Corticosteroids for the Treatment of Acute GVHD

A Randomized, Parallel-Cohort Phase 1 Study of Itacitinib in Combination With Corticosteroids for the Treatment of Acute Graft Versus Host Disease

To determine if Itacitinib in combination with corticosteroids is safe and tolerable in patients with Grade IIB-IVD acute graft-versus-host disease (GVHD).

Study Overview

• Status: Completed
• Conditions: Graft-versus-host Disease (GVHD)
• Intervention / Treatment: Drug: Itacitinib (200 mg); Drug: prednisone or methylprednisolone (corticosteroids); Drug: Itacitinib (300 mg)

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States
    • La Jolla, California, United States
    • Los Angeles, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Florida
    • Coral Gables, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kansas
    • Kansas City, Kansas, United States
    • Westwood, Kansas, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New York
    • New York, New York, United States
    • Rochester, New York, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have undergone first allo-HSCT from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies. Recipients of nonmyeloablative and myeloablative transplants are eligible.
• Clinically suspected Grades IIB to IVD acute GVHD as per modified MN-CIBMTR criteria, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.
• Subjects may, but are not required to, have previously received corticosteroids for acute GVHD:
• Evidence of myeloid engraftment. Use of growth factor supplementation is allowed.

Exclusion Criteria:

• Has received more than 1 hematopoietic stem cell transplantation.
• Has progressed on more than 2 prior treatment regimens for acute GVHD.
• Presence of an active uncontrolled infection.
• Subjects with relapsed primary disease, or subjects who have been treated for relapse after the allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was performed.
• Inadequate recovery from toxicity and/or complications from the prior allo-HSCT.
• Any corticosteroid therapy (for indications other than GVHD) at doses > 1 mg/kg per day methylprednisolone or equivalent within 7 days of randomization.
• Previously received JAK inhibitor therapy for any indication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itacitinib (200 mg); Itacitinib (200 mg) + prednisone or methylprednisolone (corticosteroids)	Drug: Itacitinib (200 mg); Other Names: INCB039110; Drug: prednisone or methylprednisolone (corticosteroids); All subjects will receive prednisone 2.5 mg/kg per day PO (or methylprednisolone 2 mg/kg IV daily) on Days 1 through 5. Subjects will be tapered as tolerated beginning on Day 6 to no less than 0.25 mg/kg per day PO (or methylprednisolone 0.2 mg/kg per day) by Day 28. After Day 28, corticosteroids should be tapered according to institutional guidelines to attain ≤ prednisone 0.2 mg/kg per day (or ≤ methylprednisolone 0.16 mg/kg per day) by Day 56.
Experimental: Itacitinib (300 mg); Itacitinib (300 mg) + prednisone or methylprednisolone (corticosteroids)	Drug: prednisone or methylprednisolone (corticosteroids); All subjects will receive prednisone 2.5 mg/kg per day PO (or methylprednisolone 2 mg/kg IV daily) on Days 1 through 5. Subjects will be tapered as tolerated beginning on Day 6 to no less than 0.25 mg/kg per day PO (or methylprednisolone 0.2 mg/kg per day) by Day 28. After Day 28, corticosteroids should be tapered according to institutional guidelines to attain ≤ prednisone 0.2 mg/kg per day (or ≤ methylprednisolone 0.16 mg/kg per day) by Day 56.; Drug: Itacitinib (300 mg); Other Names: INCB039110

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess safety and tolerability of study treatment as measured by the frequency and severity of adverse events and serious adverse events	First dose of study drug to 30 days after the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR)	Days 14, 28, 56 and 100
Maximum Observed Plasma Concentration (Cmax) of the two treatment groups Itacitinib	Day 1 and Day 7
Time to Reach the Maximum Plasma Concentration (Tmax) of the two treatment groups Itacitinib	Day 1 and Day 7
Area Under the Plasma Concentration-time Curve (AUC) of the two treatment groups Itacitinib	Day 1 and Day 7
Minimum observed plasma concentration (Cmin) of the two treatment groups Itacitinib	Day 1 and Day 7

Collaborators and Investigators

• Sponsor: Incyte Corporation

Publications and helpful links

General Publications

• Pratta M, Paczesny S, Socie G, Barkey N, Liu H, Owens S, Arbushites MC, Schroeder MA, Howell MD. A biomarker signature to predict complete response to itacitinib and corticosteroids in acute graft-versus-host disease. Br J Haematol. 2022 Aug;198(4):729-739. doi: 10.1111/bjh.18300. Epub 2022 Jun 11.
• Schroeder MA, Khoury HJ, Jagasia M, Ali H, Schiller GJ, Staser K, Choi J, Gehrs L, Arbushites MC, Yan Y, Langmuir P, Srinivas N, Pratta M, Perales MA, Chen YB, Meyers G, DiPersio JF. A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease. Blood Adv. 2020 Apr 28;4(8):1656-1669. doi: 10.1182/bloodadvances.2019001043.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: November 20, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): March 8, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Acute Graft Versus Host Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone
• Other Study ID Numbers: INCB 39110-108