Clinical trial NCT03497273: Safety of Itacitinib in Combination With Corticosteroids for Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects
Official title: An Open-Label Single-Arm Phase 1 Study Evaluating Safety of Itacitinib in Combination With Corticosteroids for the Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Graft-versus-host Disease
Keywords: JAK1 inhibitor
GVHD
acute GVHD
Japan
corticosteroids
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-04-13
Enrollment: 14
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of itacitinib in combination with corticosteroids in Japanese subjects with Grades II to IV acute graft-versus-host disease (aGVHD).


Eligibility criteria: Inclusion Criteria:

* Japanese; subject was born in Japan and has not lived outside of Japan for a total of \> 10 years, and subject can trace maternal and paternal Japanese ancestry.
* Has undergone 1 allo-hematopoietic stem cell transplant (HSCT) from any donor and source (unrelated, sibling, haploidentical donors with any matching) using bone marrow, peripheral blood or cord blood for hematologic malignancies. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
* Clinically suspected Grades II to IV aGVHD as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, occurring after allo-HSCT and any anti-GVHD prophylactic medication.
* Evidence of myeloid engraftment (eg, absolute neutrophil count \[ANC\] ≥ 0.5 × 10\^9/L for 3 consecutive assessments if ablative therapy was previously used). Use of growth factor supplementation is allowed.
* Female subjects should agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration if of childbearing potential or must have evidence of non-childbearing potential by fulfilling protocol-defined criteria at screening.

Exclusion Criteria:

* Has received more than 1 allo-HSCT.
* Has received more than 2 days of systemic corticosteroids for aGVHD.
* Presence of GVHD overlap syndrome.
* Presence of an active uncontrolled infection (defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection; persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection).
* Known human immunodeficiency virus infection.
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation. For subjects with negative HBsAg and positive total hepatitis B core antibody and for subjects who are positive for HCV antibody, HBV DNA and HCV RNA must be undetectable upon testing.
* Evidence of relapsed primary disease or having been treated for relapse after the allo-HSCT was performed.
* Any corticosteroid therapy (for indication other than GVHD) at doses \> 1 mg/kg per day methylprednisolone or equivalent within 7 days of enrollment.
* Severe organ dysfunction unrelated to underlying GVHD, including the following:

  * Cholestatic disorders or unresolved veno-occlusive disease of the liver.
  * Clinically significant or uncontrolled cardiac disease.
  * Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
* Serum creatinine \> 2.0 mg/dL or creatinine clearance \< 40 mL/min measured or calculated by Cockroft-Gault equation
* Received Janus kinase (JAK) inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
* Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Primary outcomes:
measure: Number of treatment-emergent adverse events
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Cmax of INCB039110
timeFrame: Up to approximately 1 month
measure: Cl/F of INCB039110
timeFrame: Up to approximately 1 month
measure: Objective response rate
timeFrame: Up to 100 days
measure: Nonrelapse mortality
timeFrame: Up to approximately 12 months
measure: Duration of response
timeFrame: Up to approximately 12 months
measure: Time to response
timeFrame: Up to approximately 12 months
measure: Malignancy relapse rate
timeFrame: Up to approximately 12 months
measure: Failure-free survival
timeFrame: Up to 6 months
measure: Overall survival
timeFrame: Up to approximately 12 months
Other outcomes:
Locations:
city: Anjo-Shi
country: Japan
facility: JA-Aichi Anjo Kosei Hospital
state: Aichi
city: Nagoya-Shi
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Sapporo-Shi
country: Japan
facility: Hokuyukai Sapporo Hokuyu Hospital
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Nishinomiya-Shi
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Tsukuba-shi
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki-Ken
city: Kagoshima-Shi
country: Japan
facility: Jiaikai Imamura General Hospital
state: Kagoshima
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa-Ken
city: Isehara-Shi
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: NHO Kumamoto Medical Center
state: Kumamoto-Ken
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi-Ken
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama-Ken
city: Osaka-Shi
country: Japan
facility: Osaka City University Hospital
state: Osaka
city: Nagaizumi-cho
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka-Ken
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi-Ken
city: Chuo Ku
country: Japan
facility: St. Luke's International Hospital
state: Tokyo-To
city: Minato-ku
country: Japan
facility: Jikei University Hospital
state: Tokyo-To
Study officials:
affiliation: Incyte Corporation
name: Rodica Morariu-Zamfir, MD
role: STUDY_DIRECTOR
References: