Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease

• Significant clinical response [ Time Frame: 3 and 6 months ] [ Designated as safety issue: No ]
  Assessed by decline in an affected area's skin score as measured with the Vienna Skin Scale (from 4 to 2, 3 to 1, or 2 to 0) without a concurrent increase of two or more points in another area OR by an increase in the range of motion of the shoulders, elbows or wrists by two points (in a 1-7 scale) or of the ankles by one point (in a 1 to 4 scale) without a concurrent worsening in another area.
  
  

• Proportion of patients achieving a greater than or equal to 50% reduction in the daily corticosteroid dose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Cumulative incidence of treatment failure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Defined as discontinuation of randomized treatment due to chronic GVHD progression or treatment intolerance or no significant clinical response in sclerosis.
  
  
• Number of patients achieving improvement in cutaneous sclerosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Assessed by decrease of >= 0.2 units in the Scleroderma Health Assessment Questionnaire (SHAQ).
  
  
• Correlation of blood and skin biomarker profile with each therapeutic agent and clinical response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Proportion of subjects with any percentage decline in any grade of sclerosis without increase in percentage of higher grades of sclerosis in other areas on the Vienna skin scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. To determine the best clinical response rate of cutaneous sclerosis (skin and/or fascial thickening) after 6 months of initial therapy with either Imatinib (imatinib mesylate) or Rituximab.

SECONDARY OBJECTIVES:

I. To determine the best response at either the 3 or 6 month assessment.

II. To determine the response rate at the 3 month assessment.

III. To determine the proportion of subjects who are able to taper corticosteroid after 6 months of Imatinib or Rituximab therapy.

IV. To determine the incidence of treatment failure to initial treatment with either Imatinib or Rituximab.

V. To evaluate if the Scleroderma Health Assessment Questionnaire (SHAQ) findings correlate with severity of cutaneous sclerosis clinical findings and response to study treatment.

VI. To correlate the detection of antibody against platelet derived growth factor receptor alpha(PDGFRA) with clinical response.

VII. To correlate change in B cell relevant parameters from baseline to 6 months or early crossover (antibody levels, skin collagen expression, B cell subsets) with therapeutic agent and best clinical response while on initial treatment.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive imatinib mesylate by mouth (PO) once daily (QD) for 6 months in the absence of progression of sclerosis or unacceptable toxicity. Subjects with a significant clinical response will continue to receive study drug for an additional 6 months.

ARM II: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22 (first cycle). A second cycle of treatment with rituximab is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity.

Patients with progression, treatment intolerance at any time up to 6 months, or no clinical response at 6 months will crossover to the other treatment arm.