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

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Terminated

CT.gov ID

NCT00093704

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Lymphoproliferative Disorder	Drug: bortezomib + ganciclovir	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Mar 1, 2005

Actual Primary Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib + ganciclovir 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 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.

Arm

Intervention/Treatment

Experimental: Bortezomib + ganciclovir

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

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.

Outcome Measures

Primary Outcome Measures

MTD of Bortezomib in patients with relapsed or refractory EBV + lymphomas [3 weeks]

Secondary Outcome Measures

Bortezomib in inducing lytic gene expression in EBV-infected lymphoma cells [3 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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