Chronic Graft vs. Host Disease, Corticosteroid-refractory Chronic Graft vs. Host Disease, Graft vs. Host Disease
Conditions
Keywords
cGvHD, GvHD, SR-cGvHD, ruxolitinib, INC424, Chinese adult, Pediatric, Corticosteroid, refractory
Brief summary
The purpose of the study is to assess the efficacy and safety of ruxolitinib in Chinese adult and pediatric participants aged 12 years or older with corticosteroid-refractory chronic graft vs. host disease (SR-cGvHD).
Detailed description
This is a single arm, multi-center, open label study which will enroll approximately 50 participants and investigate the efficacy and safety of ruxolitinib administered in adult and adolescent (≥12 years old) Chinese participants with SR-cGvHD. The total duration on study for an individual participant will be up to 164 weeks (approximately 3 years). The study consists of following periods, with each cycle comprised of 4 weeks (28 days): * Screening Period (Day -28 to Day -1) * Treatment period (Day 1 to Cycle 39/EOT) * Safety follow-up (Last dose +30 days) * Long-term survival follow-up period (EOT to 156 weeks on study).
Interventions
DRUGRuxolitinib
Ruxolitinib is taken orally daily at 10 mg BID, given as two 5 mg tablets.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study. * Male or female Chinese participants aged 12 or older at the time of informed consent * Able to swallow tablets.- Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible. * Evident myeloid and platelet engraftment: * Absolute neutrophil count (ANC) \>1,000/mm3 AND * Platelet count ≥25,000/mm3 Note: Use of growth factor supplementation and transfusion support is allowed during the trial, however, transfusion to reach a minimum platelet count for inclusion is not allowed during screening and at baseline. * Participants with clinically diagnosed cGvHD staging of moderate to severe according to NIH Consensus Criteria (Jagasia et al 2015) prior to Cycle 1 Day 1. * Moderate cGvHD: at least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1. * Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3. * Participants currently receiving systemic corticosteroids for the treatment of cGvHD for a duration of \< 12 months prior to Cycle 1 Day 1, and have a confirmed diagnosis of corticosteroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin et al 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows: * A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent) OR * Disease persistence without improvement despite continued treatment with prednisone at \>0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks (or equivalent) OR * Increase to prednisone dose to \>0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent) * Participants has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Exclusion criteria
For a full list of
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Cycle 7 Day 1; each Cycle =28 days | ORR is defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response, according to National Institute of Health (NIH) Consensus Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free Survival (FFS) | up to 3 years | FFS is defined as the time from the date of start of study treatment to the earliest of: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) nonrelapse mortality, or iii) addition or initiation of another systemic therapy for cGvHD. |
| Best Overall Response (BOR) | at any point up to cycle 7 day 1 (each cycle is 28 days) or the start of additional systemic therapy for cGvHD, approx. 6 months | Percentage of participants who achieved overall response (CR+PR) at any time point (up Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). |
| ORR at end of cycle 3 | end of cycle 3; each cycle = 28 days | Percentage of participants who achieved overall response (CR+PR) at Cycle 4 Day 1. |
| Duration of Response (DOR) | from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD, approx.36 months | DOR is assessed for responders only and is defined as the time from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD. |
| Overall Response (OS) | from the date of study treatment (ruxolitinib) initiation to the date of death due to any cause, approx. 36 months | OS is defined as the time from the date of study treatment (ruxolitinib) initiation to the date of death due to any cause. |
| Non-Relapse Mortality (NRM) | from date of study treatment (ruxolitinib) initiation to date of death not preceded by underlying disease relapse/recurrence, approx. 36 months | NRM is defined as the time from date of study treatment (ruxolitinib) initiation to date of death not preceded by underlying disease relapse/recurrence. |
| Malignancy Relapse/Recurrence (MR) | from date of study treatment to hematologic malignancy relapse/recurrence, approx. 36 months | Malignancy relapse/recurrence is defined as the time from date of study treatment to hematologic malignancy relapse/recurrence. |
| Reduction of daily corticosteroids dose at cycle 7 day 1 | Cycle 7 Day 1; each cycle = 28 days | Systemic corticosteroid use is the percentage of participants with \>=50% reduction from baseline in daily corticosteroid dose, the proportion of subjects with reduction from baseline to ≤ 0.2 mg/kg/day methylprednisolone (or equivalent dose of ≤ 0.25 g/kg/day prednisone or prednisolone), and subjects successfully tapered off all systemic corticosteroids at Cycle 7 Day 1, by time intervals and overall. |
Countries
China
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed