A Phase 3, Randomized, Open-Label, Multicenter Study, to Compare T-Guard to Ruxolitinib for the Treatment of Patients With Grade III or IV Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD)
Overview
- Phase
- Phase 3
- Intervention
- T-Guard
- Conditions
- Steroid-Refractory Acute Graft Versus Host Disease
- Sponsor
- Xenikos
- Enrollment
- 12
- Locations
- 48
- Primary Endpoint
- Complete Response (CR)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This is an open-label, randomized, Phase 3, multicenter trial, which has been designed to compare the efficacy and safety of T-Guard to ruxolitinib in patients with Grade III or IV Steroid-Refractory acute Graft-Versus-Host Disease (SR-aGVHD). The primary hypothesis is that T-Guard treatment will improve the Day 28 complete response (CR) rate in patients with Grades III and IV SR-aGVHD compared to ruxolitinib.
Detailed Description
Graft-vs-Host Disease (GVHD) is a complication that affects many hematopoietic stem cell transplant (HSCT) patients; it occurs when the new cells from a transplant attack the recipient's body. Acute GVHD (aGVHD) typically develops within the first three months after HSCT and is typically treated with steroid therapy. A significant fraction of the aGVHD population (10-50%) fail to respond to treatment and are deemed steroid-refractory (SR). Participants that develop Grade III or IV SR aGVHD will be randomized to receive T-Guard or ruxolitinib and will be followed for approximately 180 days. Participants will be stratified by center region (US vs. Europe) and age group (at least 55 years vs. under 55). Participants randomized to the T-Guard arm will receive 4 doses administered intravenously as four 4-hour infusions, and participants randomized to the ruxolitinib arm will receive one dose administered orally twice a day. The primary analysis will include all participants that are randomized.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible to participate in this study, patients must meet the following:
- •Patients must be at least 18.0 years of age at the time of consent.
- •Patient has undergone first allo-HSCT from any donor source or graft source. Recipients of nonmyeloablative, reduced intensity, and myeloablative conditioning regimens are eligible.
- •Patients diagnosed with Grade III/IV SR-aGVHD after allo-HSCT. SR includes aGVHD initially treated at a lower steroid dose, but must meet one of the following criteria:
- •Progressed or new organ involvement after 3 days of treatment with methylprednisolone (or equivalent) of greater than or equal to 2 mg/kg/day
- •No improvement after 7 days of primary treatment with methylprednisolone (or equivalent) of greater than or equal to 2mg/kg/day
- •Patients with visceral (GI and/or liver) plus skin aGVHD at methylprednisolone (or equivalent) initiation with improvement in skin GVHD without any improvement in visceral GVHD after 7 days of primary treatment with methylprednisolone (or equivalent) of greater than or equal to 2mg/kg/day
- •Patients who have skin GVHD alone and develop visceral aGVHD during treatment with methylprednisolone (or equivalent) of greater than or equal to 1mg/kg/day and do not improve after 3 days of greater than or equal to 2mg/kg/day Improvement or progression in organs is determined by comparing current organ staging to staging at initiation of methylprednisolone (or equivalent) treatment.
- •Patients must have evidence of myeloid engraftment (e.g., absolute neutrophil count greater than or equal to 0.5 × 109/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed.
- •Patients or an impartial witness (in case the patient is capable of providing verbal consent but not capable of signing the informed consent form (ICF)) should have given written informed consent.
Exclusion Criteria
- •Patients will be excluded from study entry if they meet any of the following exclusion criteria:
- •Patients who have a creatinine greater than or equal to 2mg/dL or estimated creatinine clearance less than 40 mL/min or those requiring hemodialysis.
- •Patients who have been diagnosed with active thrombotic microangiopathy (TMA), defined as meeting all the following criteria:
- •Greater than 4% schistocytes in blood (or equivalent if semiquantitative scale is used e.g., 3+ or 4+ schistocytes on peripheral blood smear)
- •De novo, prolonged or progressive thrombocytopenia (platelet count less than 50 x 109/L or 50% or greater reduction from previous counts)
- •Sudden and persistent increase in lactate dehydrogenase concentration greater than 2x the upper level of normal (ULN)
- •Decrease in hemoglobin concentration or increased transfusion requirement attributed to Coombs-negative hemolysis
- •Decrease in serum haptoglobin
- •Patients who have previously received treatment with eculizumab.
- •Patients who have previously received checkpoint inhibitors (either before or after allo-HCT).
Arms & Interventions
T-Guard
Participants will be administered four doses of T-Guard intravenously for a 4-hour period every other day
Intervention: T-Guard
Ruxolitinib
Participants will take ruxolitinib twice daily for continuous daily dosing
Intervention: Ruxolitinib
Outcomes
Primary Outcomes
Complete Response (CR)
Time Frame: Day 28
The primary objective of this trial is to assess the rate of CR on Day 28 post-randomization in Grades III and IV SR-aGVHD patients treated with T-Guard treatment in comparison to ruxolitinib. Participants were classified as Day 28 CR if these three conditions were satisfied: 1. Stage 0 aGVHD (no remaining symptoms) in the three target organs skin, bowel and liver, 2 . The participant is still alive at Day 28, 3 . No additional systemic treatment for aGVHD has been administered through Day 28.
Secondary Outcomes
- Overall Survival (OS)(Day 180)
- Duration of Complete Response (DoCR)(Day 28)