Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids (NRR)

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: NCT00489216
Recruitment Status : Terminated (insufficient accrual/funding withdrawn)
First Posted : June 21, 2007
Results First Posted : April 6, 2017
Last Update Posted : May 23, 2017
Genentech, Inc.
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Biological: efalizumab Not Applicable

Detailed Description:



  • 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.


  • 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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver
Study Start Date : December 2006
Actual Primary Completion Date : June 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Efalizumab
All patients on study will receive a total of 8 injections of efalizumab
Biological: efalizumab

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


Other Name: Raptiva

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Secondary Outcome Measures :
  1. Overall Complete Response Rate [ Time Frame: 57 days ]
    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.

  2. Complete Cutaneous Response Rate [ Time Frame: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab ]
    The complete disappearance of all signs of cutaneous graft-versus-host disease. Complete cutaneous response rate + partial cutaneous response rate

  3. Overall Hepatic Response Rate [ Time Frame: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab ]
    The normalization of the total serum bilirubin to <2mg/dL

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

Inclusion Criteria:

  1. 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.
  2. 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.

  3. Age ≥ 18 years
  4. 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.
  5. 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
  6. Required initial laboratory values:

Absolute neutrophil count (ANC) > 1000/μL Platelet count ≥ 20,000/μL Serum creatinine ≤ 3.0 mg/dL

Exclusion Criteria:

  1. 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.

  2. 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

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): NCT00489216

United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Genentech, Inc.
Principal Investigator: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center

Additional Information:
Responsible Party: UNC Lineberger Comprehensive Cancer Center Identifier: NCT00489216     History of Changes
Other Study ID Numbers: LCCC 0605
First Posted: June 21, 2007    Key Record Dates
Results First Posted: April 6, 2017
Last Update Posted: May 23, 2017
Last Verified: April 2017

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Graft Versus Host Disease
University of North Carolina

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs