Graft Versus Host DiseaseNRRNCT00489216
Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids
A study testing efalizumab in people with Graft Versus Host Disease, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Efalizumab may be an effective treatment for graft-versus-host disease of the skin caused by a donor stem cell transplant. PURPOSE: This clinical trial is studying the side effects and how well efalizumab works in treating patients with graft-versus-host disease of the skin that did not respond to previous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- efalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Oct 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Skin disease
- Patients must demonstrate evidence of an erythematous maculopapular rash which is felt to be clinically consistent with graft-versus-host disease. Patients must undergo skin biopsy prior to enrollment. Because the pathological findings of GVHD may be equivocal (6) a biopsy which is felt to be consistent with GVHD will be considered adequate.
- Consider sclerodermatous skin changes may be present but will not by themselves adequate for enrollment. Patients must exhibit signs of an active inflammatory rash.
- Liver disease
- Although hepatic involvement is not required for study participation, patients with concomitant GVHD of the liver are encouraged to enroll. All patients with hepatic GVHD must also demonstrate cutaneous disease. Patients with liver dysfunction are encouraged but not required to undergo hepatic biopsy in order to document that liver injury is the result of GVHD. Patients with a pretreatment serum bilirubin ≥ 2.0 mg/dL and biopsy-confirmed cutaneous GVHD will be assumed to demonstrate hepatic GVHD if no other cause for the liver function test (LFT) elevation can be identified.
- Age ≥ 18 years
Show all 16Show fewer
- Patients must be ≥ 30 days removed from allogeneic hematopoietic stem cell transplant in order to allow for engraftment. Patients receiving peripheral blood stem cells and/or bone marrow will be eligible, regardless of the degree of human leukocyte antigen (HLA) matching.
- Steroid refractory disease
- All patients must demonstrate evidence of steroid refractory graft-versus host disease of the skin or liver. In an effort to conform to a standard definition of steroid refractory disease, we will base our criteria on those described in a large intergroup trial examining the effectiveness of pentostatin for steroid refractory chronic GVHD (31). Because the present study, however, is designed to include patients with both acute and chronic GVHD based on traditional disease classification criteria, the required time intervals necessary to define steroid-refractoriness have been shortened. Patients will be considered steroid refractory if any one of the following conditions is met:
- Worsening skin or liver disease despite 1 week on the equivalent of 1mg/kg of methylprednisolone
- Failure to achieve a 50% reduction in the body surface area involved by GVHD or a 50% reduction in the total serum bilirubin after 4 weeks on the equivalent of at least 0.5 mg/kg of methylprednisolone
- Requirement of ≥ the equivalent of 0.5mg/kg of methylprednisolone to maintain a response after 8 weeks of steroid therapy
- Patients with progression of cutaneous or hepatic GVHD after a prior history of treatment with at least 8 weeks of corticosteroids now requiring the reintroduction of corticosteroids (> the equivalent of 10mg/day of methylprednisolone)
- Patients with GVHD not improving or progressing on alternative immunosuppressive agents will be eligible if steroid refractoriness has been established previously
- Required initial laboratory values:
- Absolute neutrophil count (ANC) > 1000/μL Platelet count ≥ 20,000/μL Serum creatinine ≤ 3.0 mg/dL
Who cannot join
- Non-pregnant and non-nursing
- Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential must agree to use an effective means of birth control.
- No HIV infection
- PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 2 terminal half-lives since prior and no concurrent infliximab, daclizumab, etanercept, rituximab, antithymocyte globulin (ATG), or denileukin diftitox
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
About this study
Official title: Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver
RATIONALE: Efalizumab may be an effective treatment for graft-versus-host disease of the skin caused by a donor stem cell transplant.
PURPOSE: This clinical trial is studying the side effects and how well efalizumab works in treating patients with graft-versus-host disease of the skin that did not respond to previous steroids.
Read the detailed description
OBJECTIVES:
Primary
- Assess the general safety of efalizumab in patients with cutaneous graft-vs-host disease (GVHD).
- Study the feasibility of digital imaging to objectively quantify cutaneous GVHD.
- Evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab in patients with cutaneous GVHD.
Secondary
- Assess the overall complete response rate in patients treated with this drug.
- Assess the overall cutaneous response rate (complete cutaneous response rate and partial cutaneous response rate) in patients treated with this drug.
- Assess the overall hepatic response rate (complete hepatic response rate and partial hepatic response rate) in patients treated with this drug.
- Assess the duration of any responses observed.
- Assess the effect of this drug on overall patient survival.
- Use the preliminary efficacy and toxicity data collected in this small exploratory study to decide on the appropriateness of a larger, subsequent phase II trial to more formally assess toxicity and efficacy of this drug in this patient population.
- Collect pharmacokinetic data on this drug in these patients.
OUTLINE: Patients receive efalizumab subcutaneously once weekly for 8 weeks (total of 8 doses).
Digital photographs of body regions are taken for determination of disease involved body surface area. Skin biopsies are obtained before and after treatment and analyzed for lymphocyte function associated antigen (LFA-1), intercellular adhesion molecule (ICAM-1), cluster of differentiation 4, 8, and possibly 20 (CD4, CD8, CD20) by immunohistochemistry.
After completion of study therapy, patients are followed at 1 and 9 weeks.
- Conditions
- Graft Versus Host Disease
- Being tested
- efalizumab
- Keywords
- Graft Versus Host Disease, GVHD, Efalizumab, Raptiva, Steroid, Refractory, Skin, Liver, Lineberger, University of North Carolina
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
efalizumabBiological
Also called Raptiva
Efalizumab will be administered as a subcutaneous injection once a week for 8 weeks (total of 8 doses). First efalizumab injection will be dosed at 0.7mg/kg. Subsequent weekly injections given on days 8-50 will be dosed at
1mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Efalizumab | Experimental | All patients on study will receive a total of 8 injections of efalizumab Receives: Biological: efalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Experiencing Adverse Events
The primary objective of this exploratory study is to evaluate the general tolerability of efalizumab in patients suffering from steroid refractory GVHD
Subjects will be evaluated for drug toxicity each visit. Toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) common criteria.
Measured: 120 days
Degree of Skin Involvement by GVHD Using Two Digital Photography Techniques.
Estimate of the percentage of body surface area involved by GVHD using two digital photography techniques and computerized image analyses:
- Digital photography and body surface area calculations: A total of 12 digital photographs were obtained from different body regions using systematic digital imaging and computerized image analysis.
- Body surface area calculations: Using National Institutes of Health image software, each body region will be manually traced and the total area of the traced area determined. Using a similar technique, each part of the region that is involved by a GVHD rash will also be traced and its area measured. The areas involved by rash will then be summed, and finally divided by the total area of the region. In so doing, the percentage of each region that is involved by GVHD will be determined.
Measured: 120 days
Exploratory Assessment of the Staining of Cutaneous Tissues for LFA-1, ICAM-1, CD4, CD8, and Possibly CD20
Numerical scoring system for both LFA-1 and ICAM-1 expression which could then be used in a larger phase II trial to correlate clinical response rates to pathological findings.
Measured: 57 days
Secondary outcomes (3)
Overall Complete Response Rate
To assess the overall complete response rate on study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab. A complete response (CR) was defined as the total resolution of skin disease, and a partial response was defined as >=50% reduction in the proportion of total body surface area involved by rash.
Measured: 57 days
Complete Cutaneous Response Rate
The complete disappearance of all signs of cutaneous graft-versus-host disease. Complete cutaneous response rate + partial cutaneous response rate
Measured: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab
Overall Hepatic Response Rate
The normalization of the total serum bilirubin to <2mg/dL
Measured: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2007 (estimated)
- Study startDec 2006
- Primary completionJun 2008
- Study completionOct 2008
Why it stopped: insufficient accrual/funding withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Thomas C. Shea, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00489216
- Sponsor's protocol ID
- LCCC 0605
- Acronym
- NRR
- Status last verified
- Apr 2017
- First submitted
- 20 Jun 2007
- Last updated
- 23 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver
- ClinicalTrials.gov ID
- NCT00489216
- Acronym / sponsor ID
- NRR / LCCC 0605
- Conditions
- Graft Versus Host Disease
- Keywords
- Graft Versus Host Disease, GVHD, Efalizumab, Raptiva, Steroid, Refractory, Skin, Liver
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient accrual/funding withdrawn
- Enrolment
- 2 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Dec 2006
- Primary completion
- Jun 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 21 Jun 2007 (estimated)
- Results
- Posted 6 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Efalizumab may be an effective treatment for graft-versus-host disease of the skin caused by a donor stem cell transplant.
PURPOSE: This clinical trial is studying the side effects and how well efalizumab works in treating patients with graft-versus-host disease of the skin that did not respond to previous steroids.
Detailed description
OBJECTIVES:
Primary
- Assess the general safety of efalizumab in patients with cutaneous graft-vs-host disease (GVHD).
- Study the feasibility of digital imaging to objectively quantify cutaneous GVHD.
- Evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab in patients with cutaneous GVHD.
Secondary
- Assess the overall complete response rate in patients treated with this drug.
- Assess the overall cutaneous response rate (complete cutaneous response rate and partial cutaneous response rate) in patients treated with this drug.
- Assess the overall hepatic response rate (complete hepatic response rate and partial hepatic response rate) in patients treated with this drug.
- Assess the duration of any responses observed.
- Assess the effect of this drug on overall patient survival.
- Use the preliminary efficacy and toxicity data collected in this small exploratory study to decide on the appropriateness of a larger, subsequent phase II trial to more formally assess toxicity and efficacy of this drug in this patient population.
- Collect pharmacokinetic data on this drug in these patients.
OUTLINE: Patients receive efalizumab subcutaneously once weekly for 8 weeks (total of 8 doses).
Digital photographs of body regions are taken for determination of disease involved body surface area. Skin biopsies are obtained before and after treatment and analyzed for lymphocyte function associated antigen (LFA-1), intercellular adhesion molecule (ICAM-1), cluster of differentiation 4, 8, and possibly 20 (CD4, CD8, CD20) by immunohistochemistry.
After completion of study therapy, patients are followed at 1 and 9 weeks.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Efalizumab | Experimental | Biological: efalizumabAll patients on study will receive a total of 8 injections of efalizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Skin disease
- Liver disease
- Age ≥ 18 years
- Patients must be ≥ 30 days removed from allogeneic hematopoietic stem cell transplant in order to allow for engraftment. Patients receiving peripheral blood stem cells and/or bone marrow will be eligible, regardless of the degree of human leukocyte antigen (HLA) matching.
- Steroid refractory disease
Key exclusion criteria (6 listed)
- Non-pregnant and non-nursing
- No HIV infection
- See Disease Characteristics
- At least 2 terminal half-lives since prior and no concurrent infliximab, daclizumab, etanercept, rituximab, antithymocyte globulin (ATG), or denileukin diftitox
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 |
|---|---|---|
| efalizumabAlso: RaptivaEfalizumab will be administered as a subcutaneous injection once a week for 8 weeks (total of 8 doses). First efalizumab injection will be dosed at 0.7mg/kg. Subsequent weekly injections given on days 8-50 will be dosed at 1mg/kg | Biological | Efalizumab |
Primary outcome
Number of Subjects Experiencing Adverse Events
Time frame: 120 days
The primary objective of this exploratory study is to evaluate the general tolerability of efalizumab in patients suffering from steroid refractory GVHD Subjects will be evaluated for drug toxicity each visit. Toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) common criteria.
Degree of Skin Involvement by GVHD Using Two Digital Photography Techniques.
Time frame: 120 days
Estimate of the percentage of body surface area involved by GVHD using two digital photography techniques and computerized image analyses: 1. Digital photography and body surface area calculations: A total of 12 digital photographs were obtained from different body regions using systematic digital imaging and computerized image analysis. 2. Body surface area calculations: Using National Institutes of Health image software, each body region will be manually traced and the total area of the traced area determined. Using a similar technique, each part of the region that is involved by a GVHD rash will also be traced and its area measured. The areas involved by rash will then be summed, and finally divided by the total area of the region. In so doing, the percentage of each region that is involved by GVHD will be determined.
Exploratory Assessment of the Staining of Cutaneous Tissues for LFA-1, ICAM-1, CD4, CD8, and Possibly CD20
Time frame: 57 days
Numerical scoring system for both LFA-1 and ICAM-1 expression which could then be used in a larger phase II trial to correlate clinical response rates to pathological findings.
3 secondary outcomes
Overall Complete Response Rate
Time frame: 57 days
Complete Cutaneous Response Rate
Time frame: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab
Overall Hepatic Response Rate
Time frame: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Clinical trial summary from the National Cancer Institute's PDQ® databaseLink provided by the sponsor.
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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.
Thomas C. Shea, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing efalizumab in people with Graft Versus Host Disease, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
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 16 inclusion and 6 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: stopped early, as of the sponsor's last update on 23 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects Experiencing Adverse Events (time frame: 120 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 May 2017.