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

July 29, 2020 updated by: Jonsson Comprehensive Cancer Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jonsson Comprehensive Cancer Center

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

October 6, 2004

First Submitted That Met QC Criteria

October 7, 2004

First Posted (Estimate)

October 8, 2004

Study Record Updates

Last Update Posted (Actual)

July 31, 2020

Last Update Submitted That Met QC Criteria

July 29, 2020

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000389476
  • UCLA-0403021-01
  • MILLENNIUM-VEL-04-108
  • MILLENNIUM-EBV-NHL-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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