Safety of Itacitinib in Combination With Corticosteroids for Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Japanese Subjects
- Conditions
- Acute Graft-versus-host Disease
- Interventions
- Drug: Corticosteroid
- Registration Number
- NCT03497273
- Lead Sponsor
- Incyte Corporation
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 14
- 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.
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Has received more than 1 allo-HSCT.
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Has received more than 2 days of systemic corticosteroids for aGVHD.
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Presence of GVHD overlap syndrome.
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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).
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Known human immunodeficiency virus infection.
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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.
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Evidence of relapsed primary disease or having been treated for relapse after the allo-HSCT was performed.
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Any corticosteroid therapy (for indication other than GVHD) at doses > 1 mg/kg per day methylprednisolone or equivalent within 7 days of enrollment.
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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.
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Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockroft-Gault equation
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Received Janus kinase (JAK) inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
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Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Itacitinib + corticosteroids Corticosteroid Itacitinib administered in combination with corticosteroids. Itacitinib + corticosteroids Itacitinib Itacitinib administered in combination with corticosteroids.
- Primary Outcome Measures
Name Time Method Number of treatment-emergent adverse events Up to approximately 12 months Defined as any adverse event reported for the first time or worsening of a pre-existing event after first dose of study drug.
- Secondary Outcome Measures
Name Time Method Failure-free survival Up to 6 months Defined as the proportion of participants who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic GVHD (cGVHD).
Time to response Up to approximately 12 months Defined as the interval from treatment initiation to first response.
Nonrelapse mortality Up to approximately 12 months Defined as the proportion of participants who died due to causes other than malignancy.
Duration of response Up to approximately 12 months Defined as the interval from first response until GVHD progression or death.
Malignancy relapse rate Up to approximately 12 months Defined as the proportion of participants whose underlying malignancy relapses.
Overall survival Up to approximately 12 months Defined as the interval from study enrollment to death due to any cause.
Cmax of INCB039110 Up to approximately 1 month Maximum observed plasma concentration.
Cl/F of INCB039110 Up to approximately 1 month Apparent oral dose clearance.
Objective response rate Up to 100 days Defined as the proportion of participants demonstrating a complete response, very good partial response, or partial response.
Trial Locations
- Locations (17)
JA-Aichi Anjo Kosei Hospital
🇯🇵Anjo-Shi, Aichi, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Kanagawa-Ken, Japan
Jiaikai Imamura General Hospital
🇯🇵Kagoshima-Shi, Kagoshima, Japan
Tokai University Hospital
🇯🇵Isehara-Shi, Kanagawa, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi-Ken, Japan
NHO Kumamoto Medical Center
🇯🇵Kumamoto-shi, Kumamoto-Ken, Japan
St. Luke's International Hospital
🇯🇵Chuo Ku, Tokyo-To, Japan
Okayama University Hospital
🇯🇵Okayama-shi, Okayama-Ken, Japan
Osaka City University Hospital
🇯🇵Osaka-Shi, Osaka, Japan
Jikei University Hospital
🇯🇵Minato-ku, Tokyo-To, Japan
Hokuyukai Sapporo Hokuyu Hospital
🇯🇵Sapporo-Shi, Hokkaido, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba-shi, Ibaraki-Ken, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-shi, Tochigi-Ken, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi-cho, Shizuoka-Ken, Japan
Nagoya University Hospital
🇯🇵Nagoya-Shi, Aichi, Japan
Hyogo College of Medicine Hospital
🇯🇵Nishinomiya-Shi, Hyogo, Japan