Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease
Condition: Graft Versus Host Disease; Systemic Scleroderma
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Graft vs Host Disease
Intervention: imatinib mesylate; rituximab
Intervention description: Given PO; Given IV
Intervention MeSH terms: Rituximab; Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Imatinib; Rituximab; Chronic Graft-vs-Host Disease

Summary:

      This randomized phase II trial is evaluating how well imatinib mesylate works compared to
      rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease
      (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and
      improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis within the past 18 months of cutaneous sclerosis after hematopoietic cell
             transplant (HCT) with sclerotic skin, morphea, myofascial involvement or joint
             contractures; must have a score of 2 or greater on the Vienna skin scale in any area,
             or a range-of-motion (ROM) score of 5 or less at the shoulder, elbow or wrist, or 3 or
             less at the ankle

          -  No medication added for the treatment of graft versus host disease (GVHD) within the
             past 4 weeks

          -  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

          -  Hepatitis B surface antigen positive

          -  Hepatitis B core antibody positive, unless hepatitis B virus (HBV) deoxyribonucleic
             acid (DNA) is undetectable

          -  Hepatitis C antibody positive, unless hepatitis C virus (HCV) ribonucleic acid (RNA)
             is undetectable

          -  Pregnant, lactating, or planning a pregnancy while in the study

          -  Distal leg skin score 3 or higher as the only manifestation of sclerosis

          -  Prior treatment of chronic GVHD with imatinib, rituximab, or any other monoclonal
             B-cell antibody (e.g. ofatumumab)

          -  Receipt of imatinib within the previous 6 months for any indication

          -  Receipt of any monoclonal B-cell antibody (e.g. rituximab, ofatumumab) within the
             previous 12 months for any indication

          -  Treatment with anti-B-cell cellular therapy (e.g. chimeric antigen-receptor-engineered
             cells) at any time after transplant

          -  Current treatment with extracorporeal photopheresis (ECP) at the time of enrollment

          -  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