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

• General tolerability of efalizumab
• Objective quantification of the degree of skin involvement by graft-vs-host disease (GVHD) using a digital photography technique
• Biological effects of efalizumab on cutaneous GVHD as measured by immunohistochemical assay involving staining for LFA-1, ICAM-1, CD4, CD8, and possibly CD20 both before and after treatment

• 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.

• Overall complete response rate on days 29 and 57
• Overall cutaneous response rate (complete cutaneous response rate and partial cutaneous response rate) on days 29 and 57
• Overall hepatic response rate (complete hepatic response rate and partial hepatic response rate) on days 29 and 57
• Duration of partial or complete best responses in patients demonstrating these responses
• Overall survival rate at day 120
• Determination of the appropriateness of a larger, subsequent phase II trial to more formally assess the toxicity and efficacy of efalizumab
• Pharmacokinetics as measured before the first dose of efalizumab and immediately prior to and 3 hours after the third and sixth doses

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.

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.

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