Study on the Safety and Effectiveness of VELCADE® in the Treatment of Graft-Versus-Host Disease
Condition: Graft-versus-Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Bortezomib
Intervention description: Bortezomib at 1.3 mg/m2/dose given twice weekly for two weeks followed by a 10-day rest period. If patients have a complete response, they will receive additional cycles of bortezomib.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Graft-versus-Host Disease; bortezomib

Summary:

      The purpose of this research study is to test the safety and effectiveness of VELCADE® in the
      treatment of acute graft-versus-host disease (GVHD) that has not responded to steroids or has
      worsened when the steroid dose was decreased. VELCADE® is a drug that inhibits certain immune
      reactions that happen when lymphocytes encounter foreign substances. We are doing this
      research to determine if VELCADE® may be useful in treating GVHD.
    

Eligibility criteria:

        Inclusion Criteria: (All criteria must be met)

          1. Patients must have undergone an allogeneic HSCT

          2. Clinical or histological evidence of AGVHD

          3. Has been treated with a minimum of 2mg/kg of methylprednisolone per day or equivalent
             dose of steroids and either one of the following:

               1. Has had a minimum of 3 days of steroids including the day of assignment and has
                  progressive disease.

               2. Has had a minimum of 7 days of steroids including the day of assignment and has
                  had no response.

               3. AGVHD progresses at anytime when steroids are tapered to less than 2mg/kg/day of
                  methylprednisolone or its equivalent.

          4. Performance status ECOG 0-2

          5. Patients must be willing to use contraception if they have childbearing potential

          6. Able to give informed consent

          7. Patients must be > 18 years of age, with no upper age limit.

        Exclusion Criteria: (Any one criteria will exclude patient)

          1. Performance status of ECOG >2.

          2. >Grade3 peripheral neuropathy at the time of enrollment

          3. Patient has a creatinine clearance (calculated or measured) of <30mL/min at the time
             of enrollment.

          4. Myocardial infarction within 6 months prior to enrollment or has New York Hospital
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry , any ECG
             abnormality at Screening has to be documented by the investigator/co-investigator as
             not medically relevant.

          5. Patient has hypersensitivity to bortezomib, boron or mannitol.

          6. Female subject is pregnant or breast-feeding.

          7. Patient has received other investigational drug within 14 days prior to enrollment.

          8. Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study or to obtain informed consent.