A Phase I/II open-label, single-arm, multi-center study of ruxolitinib added to corticosteroids in pediatric patients with grade II-IV acute graft vs. host disease after allogeneic hematopoietic stem cell transplantatio
- Conditions
- graft versus host disease na stamcel transplantatiegraft versus host disease
- Registration Number
- NL-OMON48950
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 4
For a full list of inclusion criteria, refer to Section 5.1. Key inclusion criteria include:
* Male or female patients age *28 days and <18 years at the time of informed
consent.
* Patients who 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 myeloablative or reduced intensity conditioning are
eligible.
* Patients with a confirmed diagnosis of grades II-IV aGvHD within 48 hours prior to
study treatment start. Biopsy confirmation of aGvHD is recommended but is not
required. Enrollment should not be delayed awaiting biopsy or pathology results.
Should the biopsy results not confirm aGvHD, however, the patient must discontinue
from the study if study treatment has already been started. Patients may have
either: Treatment-naïve aGvHD as per Table 8-2 (Harris et al. 2016) OR Steroid
refractory aGvHD as per institutional criteria, and the patient is currently receiving
systemic corticosteroids.
* Evident myeloid engraftment with ANC > 1,000/*l and platelet count >20,000/*l.
(Use of growth factor supplementation and transfusion support is allowed.)
For a full list of exclusion criteria, refer to Section 5.2. Key exclusion criteria include:
* Has received the following systemic therapy for aGvHD: a) Treatment-naïve aGvHD
patients have received any prior systemic treatment of aGvHD except for a
maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or
equivalent after the onset of acute GvHD. Patients are allowed to have received
prior GvHD prophylaxis which is not counted as systemic treatment (as long as the
prophylaxis was started prior to the diagnsosis of aGvHD);
OR
b) SR-aGvHD patients have received two or more prior systemic treatments for aGvHD in
addition to corticosteroids
* Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome
with both acute and chronic GvHD features (as defined by Jagasia et al 2015).
* Failed prior alloSCT within the past 6 months.
* Presence of relapsed primary malignancy, or who have been treated for relapse
after the alloSCT was performed, or who may require rapid immune suppression
withdrawal of immune suppression as pre-emergent treatment of early malignancy
relapse.
* Acute GvHD occurring after non-scheduled donor leukocyte infusion (DLI)
administered for pre-emptive treatment of malignancy recurrence. Note: Patients
who have received a scheduled DLI as part of their transplant procedure and not for
management of malignancy relapse are eligible.
* Any corticosteroid therapy for indications other than aGvHD at doses > 1 mg/kg/day
methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of
Screening. Routine corticosteroids administered during conditioning or cell infusion
is allowed.
* Patients who received JAK inhibitor therapy for any indication after initiation of
current alloSCT conditioning.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase I<br /><br>To assess pharmacokinetic (PK) parameters of ruxolitinib for patients with<br /><br>aGvHD and SR-aGvHD and define an age<br /><br>appropriate RP2D for each of the groups 2-4<br /><br>* Group 2: age *6y to <12y<br /><br>* Group 3: age *2y to <6y<br /><br>* Group 4: age *28days to < 2y<br /><br><br /><br>Phase II<br /><br>To measure the activity of ruxolitinib in patients with aGvHD or SR-aGvHD<br /><br>assessed by Overall Response Rate (ORR) at Day 28.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secondary endpoint is to assess the rate of durable ORR at Day 56 by<br /><br>measuring<br /><br>the proportion of all patients who achieve a CR or PR at Day 28 and maintain a<br /><br>CR or PR<br /><br>at Day 56.</p><br>