NCT00640497

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2010

Typical duration for phase_1

Geographic Reach
1 country

3 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 4, 2008

Completed
17 days until next milestone

First Posted

Study publicly available on registry

March 21, 2008

Completed
1.8 years until next milestone

Study Start

First participant enrolled

January 1, 2010

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
Last Updated

April 29, 2009

Status Verified

April 1, 2009

Enrollment Period

2 years

First QC Date

March 4, 2008

Last Update Submit

April 28, 2009

Conditions

Acute Graft Versus Host Disease

Keywords

acute GVHDimmunotoxinanti-CD3anti-CD7Ricin A

Outcome Measures

Primary Outcomes (1)

  • The acute GVHD response rate on study Day 29

    Day 29

Secondary Outcomes (8)

  • The safety and tolerability of the IT-combination, as determined by the number and intensity of adverse and serious adverse events during 12 months

    12 months

  • The acute GVHD relapse rate

    12 months

  • The incidence of chronic GVHD during 12 months

    12 months

  • The overall survival and progression free survival during 12 months

    12 months

  • The kinetics of treatment-induced T cell and Natural Killer (NK) cell depletion

    12 months

  • +3 more secondary outcomes

Study Arms (1)

1

EXPERIMENTAL

Treatment arm

Biological: IT-Combination

Interventions

IT-CombinationBIOLOGICAL

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.

1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Department of Hematology Radboud University Nijmegen (RUN)

Nijmegen, 6525 GA, Netherlands

Location

Department of Hematology Erasmus MC/Daniel den Hoed Cancer CenterGroene Hilledijk

Rotterdam, 3153075 EA, Netherlands

Location

L.F. , Department of HematologyUMC Utrecht

Utrecht, 1003584 CX, Netherlands

Location

Related Publications (1)

  • van Oosterhout YV, van Emst L, Schattenberg AV, Tax WJ, Ruiter DJ, Spits H, Nagengast FM, Masereeuw R, Evers S, de Witte T, Preijers FW. A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease. Blood. 2000 Jun 15;95(12):3693-701.

    PMID: 10845899BACKGROUND

Study Officials

  • Anton V Schattenberg,, MD, PhD,

    Department of Hematology Radboud University Nijmegen (RUN) Medical Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

March 4, 2008

First Posted

March 21, 2008

Study Start

January 1, 2010

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

April 29, 2009

Record last verified: 2009-04

Locations

NL(3)