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

Sponsor

Incyte Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT02614612

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease (GVHD)	Drug: Itacitinib (200 mg) Drug: Itacitinib (300 mg) Drug: prednisone or methylprednisolone (corticosteroids)	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Aug 1, 2018

Arms and Interventions

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: Itacitinib (300 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.

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: Itacitinib (300 mg)

Other Names:

INCB039110

Drug: prednisone or methylprednisolone (corticosteroids)

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	City	State	Country
1	Duarte	California	United States
2	La Jolla	California	United States
3	Los Angeles	California	United States
4	Denver	Colorado	United States
5	Coral Gables	Florida	United States
6	Atlanta	Georgia	United States
7	Chicago	Illinois	United States
8	Kansas City	Kansas	United States
9	Westwood	Kansas	United States
10	New Orleans	Louisiana	United States
11	Boston	Massachusetts	United States
12	Detroit	Michigan	United States
13	Saint Louis	Missouri	United States
14	Omaha	Nebraska	United States
15	New York	New York	United States
16	Rochester	New York	United States
17	Cincinnati	Ohio	United States
18	Cleveland	Ohio	United States
19	Portland	Oregon	United States
20	Hershey	Pennsylvania	United States
21	Pittsburgh	Pennsylvania	United States
22	Nashville	Tennessee	United States
23	San Antonio	Texas	United States