Clinical Trial: Anti-CD3 & Anti-CD7 Ricin A Immunotoxin-Combination for Acute Graft Versus Host Disease

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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 for the Treatment of Steroid-Resistant Acute

Brief Summary: In this study, a combination of two T-cell directed antibodies both conjugated to a cell-killing toxin will be evaluated. Previous in vitro studies have demonstrated that this so-called immunotoxin-combination (IT-combination) acts synergistically in eliminating T cells. In a subsequent clinical pilot-study, the IT-combination has generated encouraging results when applied as third line therapy. Extensive biological and clinical responses could be noted in the absence of severe acute toxicities. Building on this experience, the current study aims at evaluating the characteristics of the IT-combination when administered in an earlier phase of the disease, i.e. as second line instead of as third line therapy.

Detailed Summary:

"The experimental design is a non-controlled multicentric fixed-dose Phase I/II study. A total of 12 evaluable patients will be enrolled in 4 transplant centers throughout the Netherlands, in a 9 to 12 months period. The treatment consists of a standard dose of 4 infusions IT-combination (4 mg/m2), given 48-hours apart over a 4-hour period.

The intended follow-up period is 12 months. The patient will also be asked to participate in additional research aiming at determining the presence and evolution of biomarkers suggestive for the extent to which the IT-combination 'resets the T-cell compartment, induces clinical tolerance, and/or enhances the risk of over-immunosuppression."


Sponsor: Henogen

Current Primary Outcome: The acute GVHD response rate on study Day 29 [ Time Frame: Day 29 ]

Original Primary Outcome: The acute GVHD response rate on study Day 28 [ Time Frame: Day 28 ]

Current Secondary Outcome:

  • The safety and tolerability of the IT-combination, as determined by the number and intensity of adverse and serious adverse events during 12 months [ Time Frame: 12 months ]
  • The acute GVHD relapse rate [ Time Frame: 12 months ]
  • The incidence of chronic GVHD during 12 months [ Time Frame: 12 months ]
  • The overall survival and progression free survival during 12 months [ Time Frame: 12 months ]
  • The kinetics of treatment-induced T cell and Natural Killer (NK) cell depletion [ Time Frame: 12 months ]
  • The pharmacokinetic profile of the IT-combination [ Time Frame: day 9 ]
  • The occurrence and extent of humoral responses against the IT-combination [ Time Frame: 12 months ]
  • The occurrence of any treatment-induced cytokine release [ Time Frame: day 7 ]


Original Secondary Outcome: Same as current

Information By: Henogen

Dates:
Date Received: March 4, 2008
Date Started: January 2010
Date Completion: January 2012
Last Updated: April 28, 2009
Last Verified: April 2009