Efalizumab 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