Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids
Information source: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Graft Versus Host Disease
Intervention: efalizumab (Biological)
Phase: N/A
Status: Completed
Sponsored by: UNC Lineberger Comprehensive Cancer Center Official(s) and/or principal investigator(s): Thomas C. Shea, MD, Principal Investigator, Affiliation: UNC Lineberger Comprehensive Cancer Center
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 steroids.
Clinical Details
Official title: Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver
Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Primary outcome: Number of subjects experiencing adverse events
Secondary outcome: Feasibility of digital imagingFeasibility of serial skin biopsies Overall complete response rate
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 LFA-1,
ICAM-1, CD4, CD8, and possibly CD20 by immunohistochemistry.
After completion of study therapy, patients are followed at 1 and 9 weeks.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Diagnosis of acute or chronic cutaneous graft-versus-host disease (GVHD), as
evidenced by an erythematous maculopapular rash which is felt to be clinically
consistent with GVHD
- Pathologic findings from skin biopsy consistent with GVHD
- Sclerodermatous skin changes may be present but will not by themselves be
considered adequate for study enrollment
- Patients with concurrent hepatic GVHD are eligible
- 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 bilirubin elevation can be identified
- Underwent allogeneic hematopoietic stem cell transplantation (peripheral blood stem
cells and/or bone marrow, regardless of the degree of HLA matching) ≥ 30 days prior
to study enrollment
- Steroid refractory disease, defined by 1 of the following criteria:
- Worsening skin or liver disease despite 1 week of treatment with the equivalent
of 1 mg/kg of methylprednisolone
- Failed 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 of treatment with the
equivalent of at least 0. 5 mg/kg of methylprednisolone
- Requires the equivalent of at least 0. 5 mg/kg of methylprednisolone to maintain
a response after 8 weeks of steroid therapy
- 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 greater than 10 mg/day of methylprednisolone)
- Not improving or progressing on alternative immunosuppressive agents after prior
steroid refractoriness had been established
PATIENT CHARACTERISTICS:
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Absolute neutrophil count (ANC) > 1,000/μL
- Platelet count ≥ 20,000/μL
- Serum creatinine ≤ 3. 0 mg/dL
- 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
Locations and Contacts
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States
Additional Information
Lineberger Comprehensive Cancer Center website National Cancer Institute (NCI)
Starting date: May 2007
Last updated: February 1, 2013
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