Acute Graft Versus Host DiseasePhase 1/2NCT00640497
Anti-CD3 & Anti-CD7 Ricin A Immunotoxin-Combination for Acute Graft Versus Host Disease
A Phase 1/2 study testing IT-Combination in people with Acute Graft Versus Host Disease, run by Henogen at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Graft Versus Host Disease
- What is being tested?
- IT-Combination
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesNetherlands
- Study dates
- Jan 2010to Jan 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Department of Hematology Radboud University Nijmegen (RUN)
Nijmegen, 6525 GA
Department of Hematology Erasmus MC/Daniel den Hoed Cancer CenterGroene Hilledijk
Rotterdam, 3153075 EA
L.F. , Department of HematologyUMC Utrecht
Utrecht, 1003584 CX
About this study
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
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.
Read the 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."
- Conditions
- Acute Graft Versus Host Disease
- Being tested
- IT-Combination
- Keywords
- acute GVHD, immunotoxin, anti-CD3, anti-CD7, Ricin A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Treatment arm Receives: Biological: IT-Combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
The acute GVHD response rate on study Day 29
Measured: 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
Measured: 12 months
The acute GVHD relapse rate
Measured: 12 months
The incidence of chronic GVHD during 12 months
Measured: 12 months
The overall survival and progression free survival during 12 months
Measured: 12 months
The kinetics of treatment-induced T cell and Natural Killer (NK) cell depletion
Measured: 12 months
The pharmacokinetic profile of the IT-combination
Measured: day 9
The occurrence and extent of humoral responses against the IT-combination
Measured: 12 months
The occurrence of any treatment-induced cytokine release
Measured: day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2008 (estimated)
- Study startJan 2010
- Primary completionJan 2012 (estimated)
- Study completionJan 2012 (estimated)
Why it stopped: Unavailability of investigational product
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Anton V Schattenberg,, MD, PhD,, Principal investigator, Department of Hematology Radboud University Nijmegen (RUN) Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00640497
- Sponsor's protocol ID
- HN019/ITC-001
- Status last verified
- Apr 2009
- First submitted
- 4 Mar 2008
- Last updated
- 29 Apr 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 10845899
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00640497
- Acronym / sponsor ID
- HN019/ITC-001
- Conditions
- Acute Graft Versus Host Disease
- Keywords
- acute GVHD, immunotoxin, anti-CD3, anti-CD7, Ricin A
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unavailability of investigational product
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- HenogenIndustry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- Jan 2012 (estimated)
- Study completion
- Jan 2012 (estimated)
- First posted
- 21 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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."
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: IT-CombinationTreatment arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IT-CombinationThe 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. | Biological | 1 |
Primary outcome
The acute GVHD response rate on study Day 29
Time frame: Day 29
8 secondary outcomes
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2009.
- Background: PubMed 10845899van 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anton V Schattenberg,, MD, PhD, principal investigator
Department of Hematology Radboud University Nijmegen (RUN) Medical Centre
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IT-Combination in people with Acute Graft Versus Host Disease, run by Henogen at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 29 Apr 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The acute GVHD response rate on study Day 29 (time frame: Day 29). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00640497, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2009.