Primary: To compare the efficacy of ruxolitinib versus Investigator*s choice Best Available Therapy (BAT) in patients with moderate or severe SR-cGvHD assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 visit.Secondary: To compare the rate…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Graft versus host disease na stamcel transplantatie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall response rate
Secondary outcome
Failure free survival, change in modified Lee cGvHD Symptom Scale score. Best
overall response, duration of response, overall survival, non-relapse
mortality, proportion of patients with >=50% reduction in the daily steroid dose
at Cycle 7 Day 1, proportion of patients who successfully tapered off all
steroids at Cycle 7 Day 1. Cumulative incidence of Malignancy
Relapse/Recurrence. Change in FACT-BMT and EQ-5D. PK of ruxolitinib. Safety and
tolerability of ruxolitinib and BAT. Medical resource utilization.
Background summary
An allogenic stem cell transplantation bears the risk of the development of a
graft-versus-host disease (GvHD). In a GvHD the donor cells are acting against
the body of the patient. Immune cells of the donor attack the patient*s cells
as they are considered foreign. A chronic graft-versus-host disease (cGvHD)
develops starting from 2-3 months after the transplantation. It may last for
years. The disease may appear in all body parts. In most cases the disease is
present in the skin, liver, mouth and eyes. The disease damages tissues and
organs and weakens the immune system of the body. This is why cGvHD patients
are more susceptible for infections.
The purpose of the study is to assess the efficacy of ruxolitinib when added to
immunosuppression therapy in patients with moderate to severe corticosteroid
refractory cGvHD. The rationale of the study is based on current knowledge of
cGvHD pathophysiology and published studies that ruxolitinib impairs human
dendritic cell activation, modulates cytokine levels in dendritic cells, and
deceases Tcell proliferation in murine models. Further, published data has
shown that ruxolitinib has evidence of activity when added to immunosuppressive
therapy in patients with steroid refractory chronic graft versus host disease.
Study objective
Primary:
To compare the efficacy of ruxolitinib versus Investigator*s choice Best
Available Therapy (BAT) in patients with moderate or severe SR-cGvHD assessed
by Overall Response Rate (ORR) at the Cycle 7 Day 1 visit.
Secondary:
To compare the rate of failure free survival (FFS) and the change in the
modified Lee cGvHD Symptom Scale score between treatment groups. Other
indicators of efficacy. Cumulative incidence of Malignancy Relapse/Recurrence.
Change in FACT-BMT and EQ-5D. PK of ruxolitinib. Safety and tolerability of
ruxolitinib and BAT. Medical resource utilization.
Study design
This is a randomized open-label multi-center study of ruxolitinib versus best
available therapy (BAT). Treatment cycles of 4 weeks. Patients randomized to
the BAT arm are allowed to cross over to the ruxolitinib arm after the Cycle 7
Day 1 visit.
Maximum duration of treatment 3 years.
Follow-up for survival up to 3 years on study in subjects discontinuing study
treatment within 3 years for other reasons than complete or partial response.
Approx. 324 subjects.
Intervention
Treatment with ruxolitinib or best available therapy.
Study burden and risks
Risk: Adverse effects of ruxolitinib or best available therapy.
Burden: Cycles of 4 weeks. 4 visits during cycle 1. Visits on day 1 of every
cycle (cycle 2-7). Visits on day 1 of every 3rd cycle (cycle 9 and above).
Visit duration mostly 2-3 hours.
Physical examination: every cycle.
Blood tests (25 ml/occasion): every cycle.
Blood for biomarkers: 170 ml in total, PK 24 ml in total (extensive PK sampling
in 8 adult and 4 adolescnet subjects 64-88 ml in total).
Pulmonary function test: nearly all visits.
Dexascan (<18 yearsold): 5-6 times
Questionnaires Modified Lee Symptom Scale, FACT BMT, EQ-5D, PGIS, PGIC: nearly
every visit.
Optional biopsies during treatment from affected tissue.
Haaksbergerweg 16
Amsterdam 1101 BX
NL
Haaksbergerweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
•Female and male patients >= 12 years old.
•Having undergone allogenic stem cell transplantation, see protocol section 5
for details.
•Absolute neutrophil count > 1000/mm3 and platelet count > 25,000/ mm3.
•Patients with clinically diagnosed cGvHD staging of moderate to severe
according to NIH Consensus Criteria, see protocolsection 5 for details.
•Currently receiving systemic or topical 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 irrespective of the concomitant use of a calcineurin
inhibitor (CNI), see protocol section 5 for details.
•ECOG performance status 0-1-2 or Lansky performance score 60-100%.
•Patient must accept to be treated with only one of the following BAT (best
available therapy) options. Additions and changes are allowed during the course
of the study, but only with BAT from the following options: extracorporeal
photopheresis, low-dose methotrexate, mycophenolate mofetil, everolimus or
sirolimus, infliximab, rituximab, pentostatin, imatinib or ibrtinib.
Concomitant use of CNI and steroids is allowed.
Exclusion criteria
•Having received 2 or more systemic treatment for cGvHD in addition to
corticosteroids ± CNI for cGvHD.
•Overlap syndrome, see protocol section 5 for details.
•Treated with prior JAK inhibitors for acute GvHD, see protocol section 5 for
exceptions.
•Failed prior allogenic stem cell transplantation within the past 6 months.
•Relapsed primary malignancy, or who having been treated for relapse after the
allogenic stem cell transplantation was performed.
•History of progressive multifocal leuko-encephalopathy.
•Active uncontrolled bacterial, fungal, parasitic, or viral infection, see
protocol section 5 for details.
•Mechanical ventilation or resting O2 saturation <90%.
•Any corticosteroid therapy for indications other than cGvHD at doses >1
mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1.
•Treatment with medications that interfere with coagulation or platelet
function, see protocol section 5 for details.
•Pregnancy, lactation, insufficient contraception for females of childbearing
potential, see protocol section 5 for details.
•For male patients randomized to BAT: Sexually active males, unless they use a
condom during intercourse, see protocol section 5 for details.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201600443238-NL |
| ClinicalTrials.gov | NCT03112603 |
| CCMO | NL61887.041.17 |