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

This study has been terminated.
(study could not recruit any more patients)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00093704
First received: October 6, 2004
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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 Intervention Phase
Lymphoma
Lymphoproliferative Disorder
Drug: bortezomib + ganciclovir
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • MTD of Bortezomib in patients with relapsed or refractory EBV + lymphomas [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Bortezomib in inducing lytic gene expression in EBV-infected lymphoma cells [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: March 2005
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093704

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Sven De Vos, MD Jonsson Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00093704     History of Changes
Other Study ID Numbers: CDR0000389476, P30CA016042, UCLA-0403021-01, MILLENNIUM-VEL-04-108, MILLENNIUM-EBV-NHL-01
Study First Received: October 6, 2004
Last Updated: August 2, 2012
Health Authority: United States: Federal Government

Keywords provided by Jonsson Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Lymphoproliferative Disorders
Lymphoma
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Bortezomib
Ganciclovir
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 19, 2014