A Phase 1/2 interventional study of T-Guard in Graft vs Host Disease, sponsored by Xenikos. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-06.
Sponsored by Xenikos · Phase 1/2, Interventional, and Treatment
In this study, a combination of two antibodies both conjugated to a cell-killing toxin (so-called immunotoxins) will be evaluated. The antibodies are directed against T-cell antigens 'cluster of differentiation 3 antigen' (CD3) and CD7. Previous in vitro studies have demonstrated that this particular immunotoxin-combination, named T-Guard, acts synergistically in eliminating T cells with a preference for killing activated T-cells. In a subsequent clinical pilot-study, T-Guard has generated encouraging results when applied as third-line therapy for patients suffering form steroid-resistant acute Graft-versus-Host Disease (GVHD). Extensive biological and clinical responses could be noted in the absence of severe acute toxicities. Building on these results, the current study aims at evaluating the safety and efficacy of T-Guard for treating steroid-resistant GVHD when administered in an earlier phase of the disease process, i.e. as second-line instead of as third-line therapy.
The experimental design is a bicentric non-controlled fixed-dose Phase I/II study. A total of 20 adult patients with acute steroid-resistant GVHD will be enrolled in a 12 months period. The treatment consists of a standard dose of 4 infusions T-Guard (4 mg/m2), given 48-hours apart over a 4-hour period. The intended follow-up period is 6 months.
The primary objective is to determine the efficacy of T-Guard, 4 weeks after the first infusion (Day 28), in inducing an objective clinical response in patients with acute GVHD refractory to standard first line corticosteroid therapy.
Secondary objectives are:
Exploratory objectives are:
806 studies on the registry are indexed under Graft vs Host Disease; 138 are open to participants now.
This study's enrollment of 20 is below the median of 35 across 637 interventional studies indexed under Graft vs Host Disease.
Browse Graft vs Host Disease studies →Xenikos is the lead sponsor of 3 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Four doses of T-Guard (4 mg/m2), administered at 48-hour intervals as 4 hour infusions.
Biological: T-Guard
Also known as: Combination of SPV-T3a-RTA and WT1-RTA (equal parts, w/w)
Acute GVHD response rate
The acute GVHD response rate at 4 weeks after the first injection of T-Guard (Day 28), being defined as as the fraction of patients showing a complete or partial response (CR or PR)
Time frame: Day 28
Safety and tolerability of T-Guard
The safety and tolerability of T-Guard as assessed by evaluating Dose Limiting Toxicities (DLT's), adverse and serious adverse events reported during 6 months after initiation of treatment.
Time frame: During 6 months after initiation of treatment
Very good partial response rate
The proportion of patients achieving a very good partial response rate (VGPR) of their acute GVHD at 4 weeks after the first infusion (Day 28).
Time frame: Day 28
Acute GVHD relapse rate
Time frame: During 6 months after initiation of therapy
Incidence of chronic GVHD
Time frame: During 6 months after initiation of therapy
Overall survival and progression free survival
Time frame: During 6 months after initiation of treatment
Pharmacokinetic profile of T-Guard
* Areas under the time-concentration curves (AUC); * Peak concentration (Cmax); * Time to peak concentration (Tmax); * Terminal-phase elimination half-life (t1/2); * Apparent Clearance (CL/F); * Steady-state volume of distribution (Vss/F).
Time frame: Up to Day 9
Anti-drug-antibodies
The occurrence and extent of humoral responses against T-Guard (anti-drug-antibodies, ADA).
Time frame: Pre-treatment, Day 14, Day 28, Day 90, and Day 180
The occurrence of treatment-induced cytokine release
The occurrence of treatment-induced cytokine release, as determined by measurement of interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-a), and interferon-gamma (IFN-g) serum levels at t = 0 (pre-dose), 1 and 4 hours after starting of each infusion.
Time frame: Day 1, 3, 5, and 7
Kinetics and specificity of treatment-induced T cell and natural killer cell (NK cell) depletion
Determined by the flow cytometric assessment of the number of T-, B- and NK-cells during the first 4 weeks after initiation of treatment
Time frame: Up to Day 28
Composition and evolution of T-, B- and NK-cell compartments
The flow cytometric phenotyping of lymphocyte subsets for determine the composition and evolution of the T-, B-, and NK-cells compartments at pretreatment and at 4 weeks, 3 and 6 months after the first infusion.
Time frame: Pre-treatment, Day 28, Day 90, and Day 180
Composition and evolution of T-cell receptor (TCR) Vbeta repertoire
Time frame: Pre-treatment, Day 28, Day 90, and Day 180
The identification and evolution of host-reactive T-cell clones
Time frame: Pre-treatment, Day 28, Day 90, and Day 180
GVHD Biomarkers
Measurement of diagnostic and predictive GVHD biomarkers relative to treatment outcomes, including citrulline, C reactive protein (CRP), elafin, IL-8, tumor necrosis factor receptor 1 (TNFR1), interleukin 2 receptor-alpha (IL-2Ralpha), hepatocyte growth factor (HGF), and Reg3alpha.
Time frame: Pre-treatment, Day 14, Day 28, Day 90, and Day 180
This study is completed, as verified in Jun 2017. You cannot join it, but the record below documents what was studied.
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