corticosteroids in treatment-naive and steroid refractory- acute Graft versus Host Disease (SR-aGvHD) patients aged =>28 days to <18 years of age.
Conditions
Interventions
Group 1 : Ruxolitinib (INC424) 10 mg BID (oral)
Group 2 : Ruxolitinib (INC424) 5 mg BID (oral)
Group 3 : Ruxolitinib (INC424) 4 mg/m2 BID (oral)
Group 4 : Ruxolitinib (INC424) to be defined
Sponsors
Novartis Pharma. K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female patients age =>28 days and 1,000/microliter and platelet count >20,000/microliter. (Use of growth factor supplementation and transfusion support is allowed.)
Exclusion criteria
Exclusion criteria: Has received the following systemic therapy for aGvHD: a) Treatment-naive 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 diagnosis 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Measurement of PK parameters in aGvHD and SR-aGvHD patients: AUC, Cmax, T1/2, Ctrough using extensive PK sampling in Groups 1-3 and sparse sampling in Group 4 - Age-based determination of RP2D for each of the groups 2-4, based on observed PK parameters. - Overall response rate (ORR) at Day 28, defined as the proportion of patients demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ stage at the start of the study treatment. | — |
Countries
Europe, Japan, Oceania
Contacts
Public ContactTakamitsu Hirano
Novartis Pharma. K.K.
Outcome results
None listed