Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
Condition: Chronic Graft Versus Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: bortezomib; Prednisone
Intervention description: Given intravenously at a dose of 1.3 mg/m^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles; Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks.
Intervention MeSH terms: Prednisone; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cGVHD; Velcade; bortezomib

Summary:

      The purpose of this research study is to determine the effectiveness of bortezomib (Velcade)
      plus prednisone for treating chronic graft versus host disease (cGVHD) and the safety of this
      drug combination in this patient population. Chronic GVHD is a medical condition that may
      occur after allogeneic stem cell transplantation. The donor's immune system may recognize the
      participants body (the host) as foreign and attempt to "reject" it. Bortezomib has been used
      in other research studies, and information from those studies suggests that this drug may
      help to control the abnormal immune responses that underlie cGVHD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recipients of allogeneic stem cell transplantation with myeloablative or
             non-myeloablative conditioning regimens

          -  100 days or more past stem cell transplantation

          -  Recipients of matched or mismatched, related or unrelated adult donor stem cells

          -  Must have cGVHD requiring systemic therapy

          -  No addition or subtraction of other immunosuppressive medications. The dose of
             immunosuppressive medicines may be adjusted based on the therapeutic range of that
             drug. However, if cGVHD occurs during a taper of immune suppression, the medication(s)
             may not be increased back up to therapeutic level, but will continue a the taper dose
             for the 15 week study duration

          -  Adequate bone marrow, hepatic and renal function as outlined in the protocol

          -  Does not require hemodialysis

          -  18 years of age or older

          -  ECOG Performance Status of 0-2 or Karnofsky performance score of 70% or greater

          -  Life expectancy of more than 3 months

        Exclusion Criteria:

          -  Systemic steroid therapy in the 4 weeks prior to enrollment

          -  Active malignant disease after transplantation. Complete resection of basal cell
             carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk
             prostate cancer after curative therapy will not be considered in this category

          -  Active uncontrolled infection

          -  Peripheral neuropathy CTC Grade 1 (or greater) with pain in the 4 weeks before
             enrollment. Other neurological deficits must be reviewed with the study PI prior to
             study entry

          -  Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV
             heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
             electrocardiographic evidence of acute ischemia or active conduction system
             abnormalities

          -  Hypersensitivity to bortezomib, boron, or mannitol

          -  Female subject is pregnant or breast-feeding

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study