Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005859

Trial Description

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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.

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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.

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Organizational Data

  •   DRKS00005859
  •   2014/08/22
  •   2014/01/03
  •   no
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Secondary IDs

  •   2013-000068-27 
  •   NCT02027805  (ClinicalTrials.gov)
  •   XEN/TG-001  (Xenikos)
  •   2013-000068-27 
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Health Condition or Problem studied

  •   Graft vs Host Disease
  •   T86.02 -  message.icd10.coding.redirected.en
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Interventions/Observational Groups

  •   Biological: T-Guard
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
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Primary Outcome

- 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)

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Secondary Outcome

- 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.

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Countries of Recruitment

  •   Germany
  •   Netherlands
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Locations of Recruitment

  •  
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Recruitment

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  •   2014/01/31
  •   20
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Patients suffering from acute GVHD which is staged Grade II-IV according to the
modified Glucksberg Criteria and progressing after 3 days, or not improving after 7
days, of methylprednisolone at a dose of 2 mg/kg per day.

- Age ≥18 years.

- 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.

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Exclusion Criteria

- Patients receiving concomitant investigational therapeutics for acute GVHD, including
investigational agents used for GVHD prophylaxis, at the time of enrollment.

- Patients with signs or symptoms suggestive of chronic GVHD.

- Patients requiring mechanical ventilation, requiring vasopressor support, requiring
hemodialysis, having serum creatinine > 266 µmol/l (> 3 mg/dl), or having a serum
albumin level of 15 g/l or less.

- Patients having uncontrolled bacterial, viral or fungal infections, at the discretion
of the investigator, at the start of therapy.

- Patients with current signs or symptoms of active intrapulmonary disease.

- Patients with known hypersensitivity to any of the components of the study drug.

- Female patients who are pregnant, breast feeding, or, if sexually active, unwilling
to use effective birth control for the duration of the study.

- Male patients who are, if sexually active, unwilling to use effective birth control
for 30 days after the last infusion.

- Patients participating in a clinical trial with another investigational product
within 30 days prior to providing informed consent.

- Patients whose decision to participate might be unduly influenced by perceived
expectation of gain or harm by participation, such as patients in detention due to
official or legal order.

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Addresses

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    • Xenikos
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    • Radboudumc, Nijmegen (Netherlands)
    • Walter Van der Velden, MD, PhD 
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    • Radboudumc, Nijmegen (Netherlands)
    • Walter Van der Velden, MD, PhD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2014/11/27
* This entry means the parameter is not applicable or has not been set.