Vanderbilt-Ingram Cancer Center

Subjects are taking part in this research study because they have received a hematopoietic cell transplant (HCT). Also they have developed symptoms of cutaneous sclerosis no more than 12 months ago. About Cutaneous Sclerosis: Cutaneous sclerosis (CS) can damage skin, joints, and some internal organs. This can lead to joints freezing in permanent positions, skin sores, and difficulty breathing. CS may make it difficult to do daily activities. CS can decrease quality of life. The current way to treat CS is to use high doses of steroids which helps about half of the patients treated. Long term steroid use can result in bone damage and serious infections. Thus study doctors want to find a better way to treat CS. Purpose of the Study: The study will see if cutaneous sclerosis improves with the use of Rituximab or Imatinib. This study will also look at: -The number of subjects in the study who can lower the dose of steroids taken by mouth -The number of subjects for which Rituximab or Imatinib did not work -Whether subjects' answers to a questionnaire are helpful for CS -How Rituximab and Imatinib affects certain markers in the blood This research study is sponsored by the National Institute of Allergy and Infectious Disease (NIAID). Novartis will be providing Imatinib to study subjects assigned that treatment. Seventy-four (74) subjects are expected to be enrolled at 9 transplant centers in the United States. About 5 patients are expected to be in the study at Vanderbilt.

Criteria
 Inclusion Criteria:

 • Cutaneous sclerosis after hematopoietic cell transplant (HCT) diagnosed no more than 18 months before study enrollment with sclerotic skin, morphea, myofascial involvement or joint contractures with a score of 2 or greater on the Vienna skin scale in any area, or a score of 5 or less at the shoulder, elbow or wrist, or a score of 3 or less at the ankle on the range-of-motion (ROM) assessment

 • Stable doses of systemic immunosuppressive medications for a minimum of 4 weeks prior to the date of consent

 • Receiving corticosteroids at a dose greater than required for treatment of adrenal insufficiency, unless the physician documents why steroids are contraindicated

 • Age 2-99 years

 • Karnofsky performance status >= 60% at enrollment

 • All females of childbearing potential must have a negative serum or urine pregnancy test =< 7 days prior to starting study therapy

 • All females of childbearing potential must agree to use a form of Food and Drug Administration (FDA) approved contraception from enrollment to one month after study treatment ends

 • Subject has the ability to understand and willingness to sign a written informed consent document

 Exclusion Criteria:

 • Total bilirubin > 1.5x upper limit of normal (ULN)

 • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN

 • Renal insufficiency (serum creatinine > 2.0 mg/dl)

 • Platelets < 30,000/ul or absolute neutrophil count < 1500/ul

 • Known hypersensitivity to Rituximab or other anti-B cell antibodies

 • Known Imatinib intolerance or allergy

 • Evidence of any active viral, bacterial, or fungal infection that is progressive despite appropriate treatment

 • Known hepatitis B surface antigen positive

 • Pregnant, lactating, or planning a pregnancy while in the study

 • Distal extremity skin score 3 or higher as the only manifestation of sclerosis

 • Treatment of chronic GVHD with either Imatinib or Rituximab, or receipt of Imatinib or Rituximab within the previous 6 months for any other indication

 • History of psychiatric disorder that would interfere with normal participation in this study

 • Inability or unwillingness of subject and/or parent guardian to provide informed consent or comply with study protocol

 • Use of non-FDA approved drugs within 4 weeks of participation

 • Patient with any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements

 • Patients with uncontrolled substance abuse

 • Current treatment with sirolimus (patients may stop sirolimus on the day of enrollment; if randomized to imatinib, they should wait seven days before starting the study drug)