Efficacy and Tolerability of Entospletinib in Combination With Systemic Corticosteroids as First-Line Therapy in Adults With Chronic Graft Versus Host Disease (cGVHD)
- Registration Number
- NCT02701634
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the effect of entospletinib (ENTO) on the best overall response rate in adults with chronic graft versus host disease (cGVHD) who are currently receiving systemic corticosteroids as part of first-line therapy for cGVHD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 66
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Willing and able to provide written informed consent
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Male or non-pregnant, non-lactating, females
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Newly diagnosed cGVHD defined by:
- At least 100 days after receiving any allogeneic hematopoietic stem cell transplant AND
- Receiving a new course of systemic corticosteroids (≥ 0.5 mg/kg/day) as first-line cGVHD therapy at least 1 day and no more than 21 days prior to first dose of ENTO/Placebo AND
- Moderate to severe cGVHD as assessed by NIH cGVHD Diagnosis and Staging Criteria (NCDSC) with at least three organ systems involved OR one organ system with a score of 2 OR lung organ score = 1
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Individuals who have undergone transplant for hematologic malignancy are required to be in complete remission.
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Have either a normal ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor
Key
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Inability to begin systemic corticosteroids therapy at a dose of ≥ 0.5 mg/kg/day (or equivalent)
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Uncontrolled infection within 4 weeks prior to randomization
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History of the following therapies in the post-transplant period:
- B cell depleting biologic agents
- CD19 CAR-T cells based therapies
- BTK/SYK/JAK/PI3K inhibitors
- Phototherapy-unless administered for acute GVHD
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Treatment of cGVHD with anti-thymocyte globulins (ATG), or campath within 60 days of screening visit unless used for treatment of acute GVHD
-
Severe organ dysfunction manifested during screening period:
- Requiring supplemental oxygen at more than 2 L/min
- Uncontrolled arrhythmia or heart failure
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ENTO ENTO ENTO 400 mg or 200 mg tablet twice daily for 48 weeks Placebo Placebo Placebo to match tablet twice daily for 48 weeks
- Primary Outcome Measures
Name Time Method Best Overall Response Rate Up to 24 weeks Best overall response rate by 24 weeks was defined as the proportion of participants who achieved a complete or partial overall response as assessed by the NIH cGVHD Activity Assessment (NCAA) within 24 weeks, in the setting of add-on therapy to systemic corticosteroids as part of first-line therapy for cGVHD.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event Up to 48 weeks plus 30 days Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities Up to 48 weeks plus 30 days Failure-Free Survival Up to 48 weeks Failure-free survival was defined as the time from randomization to the earliest of first documentation of systemic therapy change, nonrelapse mortality, or recurrent malignancy.
Percentage of Participants Who Experience Any Treatment-Emergent Adverse Events (AEs) Up to 48 weeks plus 30 days Treatment-emergent adverse events are defined as 1 or both of the following: 1) any AEs with an onset on or after study drug or placebo start date and no later than earlier of 30 days after permanent discontinuation of study drug or placebo, 2) any AEs leading to premature discontinuation of study drug or placebo.
Percentage of Participants Who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline Baseline; Up to 48 weeks The percentage reduction was calculated as (systemic corticosteroid dose post baseline - baseline systemic corticosteroid dose) / baseline systemic corticosteroid dose.
Percentage of Participants Who Initiate Second-Line Therapy for cGVHD Up to 48 weeks Second-line therapy for cGVHD was defined as receiving any therapy besides systemic corticosteroids or study drug for the treatment of cGVHD. Inhaled and topical steroids are not considered second-line therapy.
Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks Baseline; Week 24 The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. A decrease from baseline value correlates with improvement in clinical outcome.
Change From Baseline in the Mouth Domain of the LSS at 24 Weeks Baseline; Week 24 The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. A decrease from baseline value correlates with improvement in clinical outcome.
Change From Baseline in the Eyes Domain of the LSS at 24 Weeks Baseline; Week 24 The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. A decrease from baseline value correlates with improvement in clinical outcome.
Change From Baseline in the Total Score of the LSS at 24 Weeks Baseline; Week 24 The LSS is a patient-reported questionnaire used to measure symptom burden. Each of the LSS subscales ranged between 0 and 100, with higher scores indicating more severe symptoms. The total score was calculated by taking the average of the subscale scores. A decrease from baseline value correlates with improvement in clinical outcome.
Duration of Response Up to 48 weeks Duration of response was defined as the time from the documentation of best overall response rate to the documentation of progressive disease. Note that flare was not considered as progressive disease in this analysis.
Trial Locations
- Locations (30)
Hopital Saint Louis
🇫🇷Paris Cedex 10, France
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Universitatsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Universitatsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Institut Paoli Calmettes
🇫🇷Marseille, Cedex 9, France
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Klinikum der Universitaet Regensburg
🇩🇪Regensburg, Germany
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Weill Cornell Medical Center
🇺🇸New York, New York, United States
Institut Gustave Roussy
🇫🇷Villejuif, France
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Kings College Hospital NHS Trust
🇬🇧London, United Kingdom
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
University of Miami
🇺🇸Miami, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Ohio State University, Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Princess Margaret
🇨🇦Toronto, Ontario, Canada