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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00640497
Recruitment Status : Withdrawn (Unavailability of investigational product)
First Posted : March 21, 2008
Last Update Posted : April 29, 2009
Information provided by:

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.

Condition or disease Intervention/treatment Phase
Acute Graft Versus Host Disease Biological: IT-Combination Phase 1 Phase 2

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."

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : January 2010
Estimated Primary Completion Date : January 2012
Estimated Study Completion Date : January 2012

Arm Intervention/treatment
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.

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

Secondary Outcome Measures :
  1. 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 ]
  2. The acute GVHD relapse rate [ Time Frame: 12 months ]
  3. The incidence of chronic GVHD during 12 months [ Time Frame: 12 months ]
  4. The overall survival and progression free survival during 12 months [ Time Frame: 12 months ]
  5. The kinetics of treatment-induced T cell and Natural Killer (NK) cell depletion [ Time Frame: 12 months ]
  6. The pharmacokinetic profile of the IT-combination [ Time Frame: day 9 ]
  7. The occurrence and extent of humoral responses against the IT-combination [ Time Frame: 12 months ]
  8. The occurrence of any treatment-induced cytokine release [ Time Frame: day 7 ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT00640497

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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
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Principal Investigator: Anton V Schattenberg,, MD, PhD, Department of Hematology Radboud University Nijmegen (RUN) Medical Centre
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Responsible Party: Sophie Houard CSO, Henogen Identifier: NCT00640497    
Other Study ID Numbers: HN019/ITC-001
First Posted: March 21, 2008    Key Record Dates
Last Update Posted: April 29, 2009
Last Verified: April 2009
Keywords provided by Henogen:
acute GVHD
Ricin A
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases