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

NCT ID: NCT00093704

Last Updated: 2020-07-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31

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.

Conditions

Lymphoma; Lymphoproliferative Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

bortezomib + ganciclovir

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sven De Vos, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Countries

United States

Other Identifiers

UCLA-0403021-01

Identifier Type: -

Identifier Source: secondary_id

MILLENNIUM-VEL-04-108

Identifier Type: -

Identifier Source: secondary_id

MILLENNIUM-EBV-NHL-01

Identifier Type: -

Identifier Source: secondary_id

CDR0000389476

Identifier Type: -

Identifier Source: org_study_id