Bortezomib Plus Rituximab for EBV+ PTLD
Condition: Post-transplant Lymphoproliferative Disease; Solid Organ Transplant; Stem Cell Transplant (Bone Marrow Transplant); Epstein Barr Virus Infections
MeSH terms: Epstein-Barr Virus Infections; Lymphoproliferative Disorders
Intervention: bortezomib; rituximab
Intervention description: Given intravenously on days 1, 4, 8 and 11 of every cycle; given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Intervention MeSH terms: Rituximab; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: bortezomib; rituximab; PTLD; EBV; transplantation

Summary:

      Post transplant lymphoproliferative disease (PTLD) is a type of B-cell non-Hodgkin lymphoma
      that occurs in patients with weakened immune systems due to immunosuppressive medications
      taken after organ or stem cell transplantation. This is usually related to a virus called
      Epstein-Barr (EPV). Rituximab is a type of drug called an "antibody" that specifically
      destroys both normal and cancerous B-cells, and is commonly used for PTLD. Bortezomib is a
      drug that has been approved by the Food and Drug Administration (FDA) to treat multiple
      myeloma and a B-cell non-Hodgkin lymphoma called Mantle Cell Lymphoma, and shows significant
      activity in lymphoma cells caused by EBV. In this research study, we hope to learn if the
      addition of bortezomib to rituximab treatment can increase the rate of complete remissions
      and cures of PTLD after organ or stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have had a prior solid organ or allogeneic stem cell transplant.

          -  Patients may be newly-diagnosed or relapsed after prior therapy

          -  Patients must have histologically confirmed CD20+ B-cell PTLD diagnosed according to
             WHO criteria. PTLD may be characterized as early lesions, PTLD/polymorphic,
             PTLD/monomorphic, or PTLD/other, all of which are eligible for this trial. B-cell PTLD
             must be associated with EBV as demonstrated either by detection of EBV antigens in
             tumor samples, or by increased EBV quantitative viral load in serum.

          -  Patients must have measurable disease

          -  18 years of age or older

          -  Estimated life expectancy of > 3 months

          -  ECOG Performance status of 0, 1, or 2

          -  Adequate organ and marrow function

          -  Women of childbearing potential and men must agree to use adequate contraception prior
             to study entry and for the duration of study participation.

        Exclusion Criteria:

          -  Patients receiving any other study agents. Patients already on prophylactic doses of
             ganciclovir or valganciclovir because of a prior history of CMV infection or because
             of risk factors for CMV infection are eligible for the study and may continue CMV
             prophylaxis.

          -  Patients with known brain metastases or central nervous system (CNS) involvement of
             their lymphoma.

          -  Patients with a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to bortezomib, rituximab, ganciclovir or
             valgancyclovir.

          -  Patients with Grade 2 or greater neuropathy within 14 days before enrollment.

          -  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.

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Pregnant or breastfeeding women

          -  Individuals with a history of malignancy are ineligible except for those outlined in
             the protocol

          -  Known HIV positive individuals

          -  Active HBV infection may be included only if they are on appropriate anti-hepatitis B
             therapy and have an undetectable HBV viral load

          -  Patient has received other investigational drugs within 14 days before enrollment

          -  Prior bortezomib