Bortezomib Plus Rituximab for EBV+ PTLD

- Both rituximab and bortezomib will be given to participants intravenously. Each cycle of
treatment will consist of 21 days. Rituximab will be given on Days 1, 8 and 15 of Cycle
1 and on Day 1 of subsequent cycles. Bortezomib will be given on Days 1, 4, 8 and 11 of
every cycle. Participants will receive a maximum of 4 cycles.

- The following study procedures will be performed during each cycle throughout the study:
Medical history review; Physical exam; Performance Status; Questionnaire; Blood draws
and; PET/CT scans (After cycles 2, 4 and 6 only).

- After Cycle 4, if the study doctor feels the participant has had a complete response to
treatment, then they will continue onto the Post-Treatment Surveillance period, which
will consist of regular clinic visits over two years.

- However, if the study doctor feels the participant has had a partial response to
treatment and that they may benefit from continuing, they will receive an additional two
cycles of bortezomib and be given daily tablets of the antiviral drug valganciclovir to
help further target EBV.

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