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

This study has been withdrawn prior to enrollment.
(Unavailability of investigational product)
Sponsor:
Information provided by:
Henogen
ClinicalTrials.gov Identifier:
NCT00640497
First received: March 4, 2008
Last updated: April 28, 2009
Last verified: April 2009
  Purpose

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.


Condition Intervention Phase
Acute Graft Versus Host Disease
Biological: IT-Combination
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Henogen:

Primary Outcome Measures:
  • The acute GVHD response rate on study Day 29 [ Time Frame: Day 29 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • The acute GVHD relapse rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • The incidence of chronic GVHD during 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • The overall survival and progression free survival during 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • The kinetics of treatment-induced T cell and Natural Killer (NK) cell depletion [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • The pharmacokinetic profile of the IT-combination [ Time Frame: day 9 ] [ Designated as safety issue: No ]
  • The occurrence and extent of humoral responses against the IT-combination [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • The occurrence of any treatment-induced cytokine release [ Time Frame: day 7 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: January 2010
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Treatment arm
Biological: IT-Combination
The treatment consists of a standard dose of 4 infusions of IT-combination (4 mg/m2), given 48-hours apart over a 4-hour period. The IT-combination is a combination of two immunotoxins. One immunotoxin is a mAb anti-CD3 conjugated to recombinant ricin A chain and the other immunotoxin is a mAb anti-CD7 conjugated to recombinant ricin A chain.

Detailed Description:

"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."

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients suffering from severe acute GVHD (Grade II-IV) progressing after 3 days, or non-improving after 5 days, of prednisolone at 2 mg/kg a day.
  • Age ≥ 18 years.
  • Patients or their guardians should have given written informed consent using forms approved by the Institutional Review Board.

Exclusion Criteria:

  • Patients receiving concomitant investigational therapeutics/prophylaxis for acute GVHD at the time of enrollment.
  • Patients with histological signs/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 20 g/l or less.
  • Patients having uncontrolled bacterial, viral or fungal infections at the start of therapy.
  • Patients with current evidence of active intrapulmonary disease.
  • Patients with known hypersensitivity to any of the components of the study drug (murine mAb or RTA).
  • Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640497

Locations
Netherlands
Department of Hematology Radboud University Nijmegen (RUN)
Nijmegen, Netherlands, 6525 GA
Department of Hematology Erasmus MC/Daniel den Hoed Cancer CenterGroene Hilledijk
Rotterdam, Netherlands, 3153075 EA
L.F. , Department of HematologyUMC Utrecht
Utrecht, Netherlands, 1003584 CX
Sponsors and Collaborators
Henogen
Investigators
Principal Investigator: Anton V Schattenberg,, MD, PhD, Department of Hematology Radboud University Nijmegen (RUN) Medical Centre
  More Information

Publications:
Responsible Party: Sophie Houard CSO, Henogen
ClinicalTrials.gov Identifier: NCT00640497     History of Changes
Other Study ID Numbers: HN019/ITC-001
Study First Received: March 4, 2008
Last Updated: April 28, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Henogen:
acute GVHD
immunotoxin
anti-CD3
anti-CD7
Ricin A

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Immunotoxins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014