A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
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
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Significant clinical response
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.
3 and 6 months
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|Froedtert and the Medical College of Wisconsin||Milwaukee, Wisconsin 53226|
|University of North Carolina at Chapel Hill||Chapel Hill, North Carolina 27599|
|Weill Cornell Medical College||New York, New York 10021|
|Stanford University Hospitals and Clinics||Stanford, California 94305|
|Dana-Farber Harvard Cancer Center||Boston, Massachusetts 02115|
|Mayo Clinic--Scottsdale||Scottsdale, Arizona 85054|
|University of Minnesota Medical Center-Fairview-Riverside||Minneapolis, Minnesota 55454-1493|