Clinical trial NCT02614612: Study of Itacitinib in Combination With Corticosteroids for the Treatment of Acute GVHD
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Graft-versus-host Disease (GVHD)
Keywords: Acute Graft Versus Host Disease
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Assess safety and tolerability of study treatment as measured by the frequency and severity of adverse events and serious adverse events
timeFrame: First dose of study drug to 30 days after the last dose of study drug
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Days 14, 28, 56 and 100
measure: Maximum Observed Plasma Concentration (Cmax) of the two treatment groups Itacitinib
timeFrame: Day 1 and Day 7
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of the two treatment groups Itacitinib
timeFrame: Day 1 and Day 7
measure: Area Under the Plasma Concentration-time Curve (AUC) of the two treatment groups Itacitinib
timeFrame: Day 1 and Day 7
measure: Minimum observed plasma concentration (Cmin) of the two treatment groups Itacitinib
timeFrame: Day 1 and Day 7
Other outcomes:
Locations:
city: Duarte
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Coral Gables
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Westwood
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Hershey
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Rodica Morariu-Zamfir, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.