A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-vs-Host Disease (BMT CTN 2002)

Stopped early · Phase 3

Conditions studied: Steroid-Refractory Acute Graft Versus Host Disease

In brief

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.

Key facts

Study ID: NCT04934670
Run by: Xenikos
People needed: 12
Starts: 2022-06-16
Expected to finish: 2023-01-19
Last updated by the study team: 2024-08-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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).
Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD.
Patients requiring mechanical ventilation or vasopressor support.
Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD or as treatment for SR-aGVHD. Reinstitution of previously used GVHD prophylaxis agents (e.g., tacrolimus, cyclosporin, methotrexate [MTX], MMF) or substitutes in cases with previously documented intolerance will be permitted. Previous treatment with a janus kinase (JAK) inhibitor as part of GVHD prophylaxis or treatment is not allowed.
Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl.
Patients who have a creatine kinase (CK) level of greater than 5 times the upper limit of normal.
Patients with uncontrolled infections. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. Progression of infection is defined as:
hemodynamic instability attributable to sepsis OR
new symptoms attributable to infection OR
worsening physical signs attributable to infection OR
worsening radiographic findings attributable to infection Patients with radiographic findings attributable to infection within 4 weeks prior to enrollment must have a repeat radiographic exam within one week of enrollment that documents absence of worsening.
Patients with evidence of relapsed, progressing, or persistent malignancy, or who have been treated for relapse after transplant, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression.
Patients with unresolved serious toxicity or complications (other than aGVHD) due to previous transplant.
History of sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD).
Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA).

Where it is running

University of Alabama — Birmingham, Alabama, United States
City of Hope National Medical Center — Duarte, California, United States
H. Lee Moffitt Cancer Center — Tampa, Florida, United States
Washington University St. Louis — St Louis, Missouri, United States
Mount Sinai Medical Center — New York, New York, United States
Duke University Medical Center — Durham, North Carolina, United States
Wake Forest University — Winston-Salem, North Carolina, United States
Ohio State University — Columbus, Ohio, United States
Oregon Health & Science University — Portland, Oregon, United States
Sarah Cannon Research Institute — Nashville, Tennessee, United States
University of Utah — Salt Lake City, Utah, United States
University of Wisconsin — Madison, Wisconsin, United States
Site BE300 — Brussels, Belgium
Site BE301 — Brussels, Belgium
Site BE307 — Ghent, Belgium
Site BE305 — Leuven, Belgium
Site BE302 — Liège, Belgium
Site BE303 — Yvoir, Belgium
Site HR320 — Zagreb, Croatia
Site FR341 — Angers, France
Site FR345 — Créteil, France
Site FR346 — La Tronche, France
Site FR355 — Lille, France
SiteFR354 — Nantes, France
SiteFR342 — Paris, France

Full record on ClinicalTrials.gov

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