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.

Condition	Treatment or Intervention
recurrent adult Hodgkin's lymphoma recurrent adult Burkitt's lymphoma post-transplant lymphoproliferative disorder recurrent adult grade III lymphomatoid granulomatosis angioimmunoblastic T-cell lymphoma adult grade III lymphomatoid granulomatosis	Drug: bortezomib  Drug: ganciclovir  Procedure: antiviral therapy  Procedure: enzyme inhibitor therapy

Further Study Details: 

OBJECTIVES: Primary

• Determine the safety and tolerability of bortezomib and ganciclovir 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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
• No primary or secondary CNS lymphoma or HIV-related lymphoma
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• 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

Cardiovascular

• No myocardial infarction within the past 6 months
• No acute ischemia or new conduction system abnormalities by electrocardiogram
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not hospitalized
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other uncontrolled illness
• No ongoing or active systemic infection
• No psychiatric illness or social situation that would preclude study compliance
• No history of allergic reaction attributable to compounds of similar chemical or biological composition to study drugs
• No sensitivity to boron, mannitol, bortezomib, or ganciclovir

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 4 weeks since prior immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy

Endocrine therapy

• No concurrent corticosteroids (≥ 10 mg of prednisone or equivalent)

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

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

Other

• Recovered from all prior therapy
• At least 4 weeks since prior investigational agents
• No other concurrent anticancer therapy
• No other concurrent investigational agents

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095,  United States; Recruiting

Study chairs or principal investigators

Sven De Vos, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000389476; UCLA-0403021-01; MILLENNIUM-VEL-04-108; MILLENNIUM-EBV-NHL-01; NCT00093704
Record last reviewed:  September 2004
Last Updated:  February 24, 2005
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093704
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08