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)
- Conditions
- N/A1001884910027665
- Registration Number
- NL-OMON50082
- Lead Sponsor
- Xenikos B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
1. Patients must be at least 18.0 years of age at the time of consent.
2. Patient has undergone first allo-HSCT from any donor source or graft source.
3. Patients diagnosed with Grade III or 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
4. 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.
5. Patients or an impartial witness (in case the patient is capable to provide
verbal consent but not capable to sign the informed consent) should have given
written informed consent.
1. 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.
2. 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 ULN,
• decrease in hemoglobin concentration or increased transfusion requirement
attributed to Coombs-negative hemolysis, AND
• decrease in serum haptoglobin
3. Patients who have previously received treatment with eculizumab.
4. Patients who have previously received checkpoint inhibitors (either before
or after allo-HCT).
5. Patients who have been diagnosed with overlap syndrome, that is, with any
concurrent features of cGVHD.
6. Patients requiring mechanical ventilation or vasopressor support.
7. 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, MTX,
MMF) or substitutes in cases with previously documented intolerance will be
permitted. Previous treatment with a JAK inhibitor as part of GVHD prophylaxis
or treatment is not allowed.
8. Patients who have severe hypoalbuminemia, with an albumin of less than or
equal to 1 g/dl.
9. Patients who have a creatine kinase (CK) level of greater than 5 times the
upper limit of normal.
10. 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
11. 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.
12. Patients with evidence of minimal residual disease requiring withdrawal of
systemic immune suppression.
13. Patients with unresolved serious toxicity or complications (other than
acute GVHD) due to previous transplant.
14. History of sinusoidal obstruction syndrome (SOS)/veno-occlusive disease
(VOD).
15. Patients with known hypersensitivity to any of the components murine
monoclonal antibodies (mAb) or recombinant Ricin Toxin A-chain (RTA).
16. Patients who have had treatment with any other investigational agent,
device, or procedure within 21 days (or 5 half-lives, whichever is greater)
prior to enrollment.
17. Patients who have received more than one allo-HSCT.
18. Patients with known human immunodeficiency virus infection.
19. Patients who
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the rate of complete response (CR) in Grades III and IV SR-aGVHD<br /><br>participants on Day 28 postrandomization.</p><br>
- Secondary Outcome Measures
Name Time Method