Safety and Efficacy Study of T-Guard to Treat Steroid-resistant Acute GVHD
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|ClinicalTrials.gov Identifier: NCT02027805|
Recruitment Status : Completed
First Posted : January 6, 2014
Last Update Posted : June 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Graft vs Host Disease||Biological: T-Guard||Phase 1 Phase 2|
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:
- To evaluate the overall safety and efficacy of T-Guard during the first 6 months after imitation of therapy;
- To determine the pharmacokinetic profile of T-Guard;
- To determine the immunogenicity of T-Guard.
Exploratory objectives are:
- To study the specificity and kinetics of the treatment-induced depletion and subsequent repopulation of lymphocyte subsets;
- To evaluate diagnostic and predictive GVHD biomarkers relative to treatment outcomes.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Multicentric Study to Determine the Safety and Efficacy of a Combination of Anti-CD3 & Anti-CD7 Ricin A Immunotoxins (T-Guard) for the Treatment of Steroid-resistant Acute Graft-versus-Host Disease.|
|Actual Study Start Date :||March 5, 2014|
|Actual Primary Completion Date :||September 7, 2016|
|Actual Study Completion Date :||November 3, 2016|
Four doses of T-Guard (4 mg/m2), administered at 48-hour intervals as 4 hour infusions.
Other Name: Combination of SPV-T3a-RTA and WT1-RTA (equal parts, w/w)
- Acute GVHD response rate [ Time Frame: Day 28 ]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)
- Safety and tolerability of T-Guard [ Time Frame: During 6 months after initiation of treatment ]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.
- Very good partial response rate [ Time Frame: Day 28 ]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).
- 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 [ Time Frame: Up to Day 9 ]
- 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).
- Anti-drug-antibodies [ Time Frame: Pre-treatment, Day 14, Day 28, Day 90, and Day 180 ]The occurrence and extent of humoral responses against T-Guard (anti-drug-antibodies, ADA).
- The occurrence of treatment-induced cytokine release [ Time Frame: Day 1, 3, 5, and 7 ]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.
- Kinetics and specificity of treatment-induced T cell and natural killer cell (NK cell) depletion [ Time Frame: Up to Day 28 ]Determined by the flow cytometric assessment of the number of T-, B- and NK-cells during the first 4 weeks after initiation of treatment
- Composition and evolution of T-, B- and NK-cell compartments [ Time Frame: Pre-treatment, Day 28, Day 90, and Day 180 ]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.
- 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 [ Time Frame: Pre-treatment, Day 14, Day 28, Day 90, and Day 180 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02027805
|University Hospital Münster|
|Münster, North Rhine-Westphalia, Germany, 48149|
|Nijmegen, Gelderland, Netherlands, 6525 GA|
|Principal Investigator:||Walter Van der Velden, MD, PhD||Radboudumc, Nijmegen (Netherlands)|
|Principal Investigator:||Matthias Stelljes, MD, PhD||Unversity Hospital Münster, Münster (Germany)|