Bortezomib and Ganciclovir in Treating Patients With Relapsed or Refractory Epstein Barr Virus-Positive Lymphoma

OBJECTIVES:

Primary

- Maximum Tolerated Dose (MTD) of bortezomib in patients with relapsed or refractory
Epstein Barr virus-positive lymphoma.

Secondary

- Assess the antitumor effect of this regimen in these patients.

OUTLINE: This is a pilot, open-label, dose-escalation study of bortezomib.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11. Patients also
receive ganciclovir IV twice daily on days 1-14. Treatment repeats every 21 days for a
maximum of 3 courses.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-9 patients will be accrued for this study.

Inclusion Criteria:

- Histologically confirmed Epstein Barr virus-positive lymphoma, including the
following subtypes:

- Post-transplantation lymphoma

- Burkitt's lymphoma

- Hodgkin's lymphoma

- T-/NK-cell lymphoma

- Unresponsive to, or relapsed after, at least 1 prior chemotherapy regimen

- Bidimensionally measurable disease by CT scan

- At least 1 lesion ≥ 1.5 cm in the greatest diameter

- Age 18 and over

- ECOG 0-2 OR

- Karnofsky 50-100%

- Life expectancy More than 3 months

- Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3 (no growth factor support within the past
4 weeks)

- Hemoglobin ≥ 9.0 g/dL

- Platelet count ≥ 50,000/mm^3 (no platelet transfusions within the past 4 weeks)

- Hepatic

- Bilirubin ≤ 2.0 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN (5 times ULN in patients with liver involvement)

- No active hepatitis B or C

- Renal

- Creatinine clearance ≥ 60 mL/min

- Sodium > 130 mmol/L

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- At least 4 weeks since prior immunotherapy

- At least 4 weeks since prior chemotherapy

- At least 4 weeks since prior radiotherapy

- More than 4 weeks since prior major surgery unless fully recovered

- Recovered from all prior therapy

- At least 4 weeks since prior investigational agents

Exclusion Criteria:

- primary or secondary CNS lymphoma or HIV-related lymphoma

- known brain metastases

- myocardial infarction within the past 6 months

- acute ischemia or new conduction system abnormalities by electrocardiogram

- symptomatic congestive heart failure

- unstable angina pectoris

- cardiac arrhythmia

- hospitalized

- pregnant or nursing

- other uncontrolled illness

- ongoing or active systemic infection

- psychiatric illness or social situation that would preclude study compliance

- history of allergic reaction attributable to compounds of similar chemical or
biological composition to study drugs

- sensitivity to boron, mannitol, bortezomib, or ganciclovir

- concurrent corticosteroids (≥ 10 mg of prednisone or equivalent)

- concurrent radiotherapy

- other concurrent anticancer therapy

- other concurrent investigational agents