This is a parallel, Phase 3, two-arm study for the treatment of newly diagnosed moderate or severe chronic GVHD. The study duration for a participant includes up to 4 weeks for screening; a treatment period until clinically meaningful cGVHD progression (defined as progression requiring addition of new systemic treatment for cGVHD), relapse/recurrence of the underlying disease, participant starts new systemic treatment for cGVHD or experiences an unacceptable toxicity, at the request of the participants or the investigators, or until the end of study is reached, whichever comes first; at least 30 days follow-up of adverse events (AEs) after the last dose until resolution or stabilization, if applicable; and long-term follow-up until death or study close-out, whichever comes first.
Up to 2.5 years
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
260
Pharmaceutical form:Tablet-Route of administration:oral
Pharmaceutical form:Table-Route of administration:oral
Pharmaceutical form:Tablet-Route of administration:oral
Pharmaceutical form:Tablet-Route of administration:oral
University of Arkansas for Medical Sciences-Site Number : 8400019
Little Rock, Arkansas, United States
City of Hope National Medical Center- Site Number : 8400001
Duarte, California, United States
University of California San Francisco - Parnassus Heights- Site Number : 8400035
San Francisco, California, United States
AdventHealth Orlando- Site Number : 8400023
Orlando, Florida, United States
The Hope Clinic of Emory University- Site Number : 8400020
Decatur, Georgia, United States
Event-Free Survival (EFS)
From the date of randomization to the date of any predefined event, whichever occurs first
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Modified Lee Symptom Scale (mLSS)
Proportion of participants who achieve a clinically relevant reduction in mLSS of at least 6 points from baseline (Only in participants at least 18 years of age)
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Durable overall response rate
Proportion of participants who achieve an overall response (PR or CR) as per 2014 NIH consensus response criteria by 48 weeks and maintained the response for a duration of at least 6 months
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Rate of corticosteroid withdrawal
Proportion of participants who successfully discontinue all systemic corticosteroids for cGVHD for at least 30 days before the occurrence of cGVHD progression, or start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or unacceptable toxicity
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Overall response rate (ORR)
Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria at any time before the start of new systemic treatment for cGVHD
Time frame: Until the end of the study (up to 2.5 years since first patient in).
ORR by 24 weeks
Proportion of participants who achieve an overall response (CR or PR) as per 2014 NIH consensus response criteria by 24 weeks (Cycle 7 Day 1) before the start of new systemic treatment for cGVHD
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Duration of response (DOR)
Time from the date of the first response to the date of cGVHD progression, start of new systemic treatment for cGVHD, or death, whichever occurs first. DOR is determined only for participants who achieved overall response (PR or CR) as per 2014 NIH consensus response criteria
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Dose reduction in corticosteroid
Proportion of participants with a reduction in daily corticosteroid dose
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Failure Free Survival (FFS)
Failure Free Survival (FFS) is defined as the time from the date of randomization to the date of start of a new systemic treatment for cGVHD, relapse or recurrence of the underlying disease, or death, whichever occurs first.
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Change in patient reported outcome (PRO)
Change from baseline in Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) (Only in participants at least 18 years of age) and the European Quality of Life Group Questionnaire with 5 Dimensions and 5 Levels (EQ5D5L)
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Number of participants with treatment-emergent adverse events [TEAEs], serious TEAEs, and adverse events of special interest (AESIs)
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Overall survival
The time from the date of randomization to the date of death due to any cause
Time frame: Until the end of the study (up to 2.5 years since first patient in).
Time to response (TTR)
Time to Response is defined as the time from randomization to the date the patient has first response (CR or PR).
Time frame: Until the end of study (up to 2.5 years since first patient in)
Response by organ
Proportion of participants who achieve CR or PR as per NIH consensus response criteria (2014) at any time point in each involved organ and before the start of a new systemic therapy for cGVHD.
Time frame: Until the end of study (up to 2.5 years since first patient in)
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Northwestern University- Site Number : 8400017
Chicago, Illinois, United States
Indiana University Health University Hospital- Site Number : 8400006
Indianapolis, Indiana, United States
University of Kentucky Chandler Medical Center- Site Number : 8400024
Lexington, Kentucky, United States
Johns Hopkins Hospital- Site Number : 8400033
Baltimore, Maryland, United States
Dana Farber Cancer Institute Site Number : 8400005
Boston, Massachusetts, United States
...and 141 more locations