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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00489216
First received: June 20, 2007
Last updated: February 1, 2013
Last verified: February 2013
  Purpose

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 Intervention
Graft Versus Host Disease
Biological: efalizumab

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of subjects experiencing adverse events [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]

    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 NCTCAE common criteria.



Secondary Outcome Measures:
  • Feasibility of digital imaging [ Time Frame: 120 days ] [ Designated as safety issue: No ]
    To study the feasibility of digital imaging to objectively quantify cutaneous GVHD.

  • Feasibility of serial skin biopsies [ Time Frame: 57 days ] [ Designated as safety issue: No ]
    To evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab therapy in patients with cutaneous GVHD.

  • Overall complete response rate [ Time Frame: 57 days ] [ Designated as safety issue: No ]
    To assess the overall complete response rate on study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab.


Enrollment: 2
Study Start Date: May 2007
Study Completion Date: October 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

1mg/kg

Other Name: Raptiva

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489216

Locations
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
Investigators
Principal Investigator: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00489216     History of Changes
Other Study ID Numbers: LCCC 0605, CDR0000550090
Study First Received: June 20, 2007
Last Updated: February 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Graft Versus Host Disease
GVHD
Efalizumab
Raptiva
Steroid
Refractory
Skin
Liver
Lineberger
University of North Carolina

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

ClinicalTrials.gov processed this record on July 23, 2014