Study of activity, safety and pharmacokinetics in pediatric subjects with moderate and severe chronic graft vs. host disease after allogeneic stem cell transplant.

JRCT ID: jRCT2080225240

Registered date:23/06/2020

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: corticosteroids in treatment-naive and steroid refractory- with moderate to severe chronic Graft versus Host Disease (SR-aGvHD) patients aged =>28 days to <18 years of age.
• Date of first enrollment: 31/08/2020
• Target sample size: 42
• Countries of recruitment: Japan,Europe,Oceania
• Study type: Interventional

Intervention(s)

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

Outcome(s)

• Primary Outcome: Overall response rate (ORR) at Cycle 7 Day 1, defined as the proportion of subjects 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. The response is assessed per NIH consensus criteria, and scoring of response will be relative to the organ stage at the start of study treatment.

Key inclusion & exclusion criteria

• Age minimum: >= 4weeks old
• Age maximum: <= 17age old
• Gender: Both

Include criteria

- Male or female subjects age => 28 days and < 18 years at the time of informed consent.
- Subjects who have undergone alloSCT from any donor source (matched unrelated donor, sibling and haplo-identical) using bone marrow (BM), peripheral blood stem cells, or cord blood. Recipients of myeloablative or reduced intensity conditioning are eligible.
- Subjects with diagnosed moderate to severe cGvHD according to NIH Consensus Criteria prior to Cycle 1 Day 1. Subjects must be either:
- Treatment-naive cGvHD subjects that have not received any prior systemic treatment for cGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of chronic GvHD. Subjects are allowed to have received prior systemic therapy for cGvHD prophylaxis (as long as the prophylaxis was started prior to the diagnosis of cGvHD),
OR
- Steroid refractory (SR) moderate to severe cGvHD as per institutional criteria, or per physician decision in case institutional criteria are not available, and still receiving systemic corticosteroids for the treatment of cGvHD for a duration of < 18 months prior to Cycle 1 Day 1.

Exclude criteria

- For a full list of exclusion criteria, refer to Key exclusion criteria include:
- SR-cGvHD subjects with a prior cGvHD treatment with a janus kinase (JAK1) or a JAK2- or a JAK1/2-inhibitor are not allowed, except when the subject achieved complete or partial response and has been off JAK inhibitor treatment for at least 4 weeks prior to Cycle 1 Day 1 or up to 5 times the half-life of the prior JAK inhibitor, whichever is longer.
- Failed prior alloSCT within the past 6 months; subjects with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed, or who require withdrawal of immune suppression as pre-emergent treatment of early malignancy relapse.
- Subjects who initiated systemic calcineurin inhibitors (CNI; cyclosporine or tacrolimus) within 3 weeks prior to start of ruxolitinib on Cycle 1 Day 1. Note: Systemic CNI are allowed when initiated > 3 weeks from start of ruxolitinib.
- Significant respiratory disease including subjects who are on mechanical ventilation or who have a resting oxygen saturation < 90% by pulse-oximetry on room-air.
- Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to cGvHD and ongoing organ dysfunction)
- Presence of clinically active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
- Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of screening visit.
- Current therapy with medications that interfere with coagulation or platelet function, including but not limited to aspirin and related drugs, heparin, and warfarin (to minimize risk of bleeding).
- Subject is receiving fluconazole at daily doses higher than 6 mg/kg (maximum 200 mg).
- Presence of severely impaired renal function (confirmed within 72h prior to ruxolitinib start) defined by:
- Glomerular Filtration Rate (GFR) < 30 mL/min/1.73 m2, using estimated creatinine clearance (CLcr) calculated by updated bedside Schwartz equation or Cockroft Gault equation
Or
- renal dialysis requirement

Related Information

• Primary Sponsor: Novartis Pharma. K.K.
• Source(s) of Monetary Support: -
• Secondary ID(s): NCT03774082,JapicCTI-205336