Safety and Efficacy Study of T-Guard to Treat Steroid-resistant Acute GVHD

NCT02027805 | Completed Phase 1 DMC

• 2 other identifiers: XEN/TG-0012013-000068-27
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Graft vs Host Disease

Keywords

Steroid-resistant; Graft vs Host Disease; Refractory acute Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Allogeneic Stem Cell Transplantation; Immune System Diseases; Antibodies, monoclonal; Immunotoxins; Immunosuppressive agents

Outcome Measures

Primary Outcomes (1)

• 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)

  Day 28

Secondary Outcomes (8)

• Safety and tolerability of T-Guard

  During 6 months after initiation of treatment

• Very good partial response rate

  Day 28

• Acute GVHD relapse rate

  During 6 months after initiation of therapy

• Incidence of chronic GVHD

  During 6 months after initiation of therapy

• Overall survival and progression free survival

  During 6 months after initiation of treatment

Other Outcomes (5)

• Kinetics and specificity of treatment-induced T cell and natural killer cell (NK cell) depletion

  Up to Day 28

• Composition and evolution of T-, B- and NK-cell compartments

  Pre-treatment, Day 28, Day 90, and Day 180

• Composition and evolution of T-cell receptor (TCR) Vbeta repertoire

  Pre-treatment, Day 28, Day 90, and Day 180

Study Arms (1)

T-Guard

EXPERIMENTAL

Four doses of T-Guard (4 mg/m2), administered at 48-hour intervals as 4 hour infusions.

Biological: T-Guard

Interventions

T-Guard BIOLOGICAL

Also known as: Combination of SPV-T3a-RTA and WT1-RTA (equal parts, w/w)

T-Guard

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xenikos: lead

Study Sites (2)

University Hospital Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

MeSH Terms

Conditions

Graft vs Host Disease; Immune System Diseases

Study Officials

• Walter Van der Velden, MD, PhD

  Radboudumc, Nijmegen (Netherlands)

  PRINCIPAL INVESTIGATOR

• Matthias Stelljes, MD, PhD

  Unversity Hospital Münster, Münster (Germany)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2014
• First Posted: January 6, 2014
• Study Start: March 5, 2014
• Primary Completion: September 7, 2016
• Study Completion: November 3, 2016
• Last Updated: June 6, 2017

Record last verified: 2017-06

Locations

DE (1); NL (1)