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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. The Epstein Barr virus can cause cancer and lymphoproliferative disorders. Ganciclovir is an antiviral drug that acts against the Epstein Barr virus. Giving ganciclovir together with bortezomib may kill more Epstein Barr virus-infected cancer cells. PURPOSE: This clinical trial is studying how well giving bortezomib together with ganciclovir works in treating patients with relapsed or refractory Epstein Barr virus-positive lymphoma.

Detailed Description
-----------------
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.

Official Title
-----------------
EBV as Therapeutic Target: A Pilot Study of Inducing and Targeting EBV-TK in EBV-Positive Lymphomas by Combination of Bortezomib and Ganciclovir

Conditions
-----------------
Lymphoma, Lymphoproliferative Disorder

Intervention / Treatment
-----------------
* Drug: bortezomib + ganciclovir


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib + ganciclovir<br>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. | Drug: bortezomib + ganciclovir<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD of Bortezomib in patients with relapsed or refractory EBV + lymphomas |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bortezomib in inducing lytic gene expression in EBV-infected lymphoma cells |  | 3 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent adult Hodgkin lymphoma, recurrent adult Burkitt lymphoma, post-transplant lymphoproliferative disorder, recurrent adult grade III lymphomatoid granulomatosis, angioimmunoblastic T-cell lymphoma, adult grade III lymphomatoid granulomatosis