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Ganciclovir Plus Arginine Butyrate in Treating Patients With Cancer or Lymphoproliferative Disorders Associated With the Epstein Barr Virus

Primary Purpose

Leukemia, Lymphoma, Precancerous Condition

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
arginine butyrate
ganciclovir
Sponsored by
Boston Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, small intestine lymphoma, childhood immunoblastic large cell lymphoma, grade I lymphomatoid granulomatosis, grade II lymphomatoid granulomatosis, adult grade III lymphomatoid granulomatosis, recurrent adult grade III lymphomatoid granulomatosis, childhood grade III lymphomatoid granulomatosis, recurrent childhood grade III lymphomatoid granulomatosis, recurrent grade I lymphomatoid granulomatosis, recurrent grade II lymphomatoid granulomatosis, stage II childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage I adult Burkitt lymphoma, T-cell large granular lymphocyte leukemia, stage II grade 1 follicular lymphoma, stage II grade 2 follicular lymphoma, stage II grade 3 follicular lymphoma, stage II adult diffuse small cleaved cell lymphoma, stage II adult diffuse mixed cell lymphoma, stage II adult diffuse large cell lymphoma, stage II adult immunoblastic large cell lymphoma, stage II adult lymphoblastic lymphoma, stage II adult Burkitt lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, stage I childhood small noncleaved cell lymphoma, stage I childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood large cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, stage II mantle cell lymphoma, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage I marginal zone lymphoma, stage I small lymphocytic lymphoma, stage II small lymphocytic lymphoma, stage II marginal zone lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed malignancy or lymphoproliferative disease including the following: Nasopharyngeal carcinoma Hodgkin's lymphoma African Burkitt's lymphoma T-cell non-Hodgkin's lymphoma B-cell non-Hodgkin's lymphoma if Epstein Barr Virus (EBV) positive Other lymphomas associated with immunodeficiency or immunosuppression, including AIDS-related lymphoma B-cell lymphoproliferative disorders Monoclonal or oligoclonal B-cell lymphoid disease (no polyclonal disease) EBV positive by immunohistochemistry or in situ hybridization Negative serology for EBV allowed PATIENT CHARACTERISTICS: Age: 3 and over Performance status: Any status Hematopoietic: Absolute granulocyte count at least 1,000/mm^3 Platelet count at least 50,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL Aminotransferase less than 2 times normal Renal: Creatinine less than 3.0 mg/dL Creatinine clearance greater than 30 mL/min Cardiovascular: No acute myocardial infarction within the past 6 months No atrial fibrillation within the past 6 months Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Prior bone marrow or stem cell transplantation allowed No concurrent immunotherapy No concurrent interferon or tacrolimus Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered No concurrent cytotoxic chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: Recovered from prior radiotherapy Surgery: Not specified

Sites / Locations

  • Methodist Cancer Center at Methodist Hospital
  • Cancer Research Center at Boston Medical Center
  • Memorial Sloan-Kettering Cancer Center
  • Hopital Necker
  • Medizinische Hochschule Hannover
  • Istituto Nazionale per lo Studio e la Cura dei Tumori

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
October 4, 2000
Last Updated
July 25, 2013
Sponsor
Boston Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00006340
Brief Title
Ganciclovir Plus Arginine Butyrate in Treating Patients With Cancer or Lymphoproliferative Disorders Associated With the Epstein Barr Virus
Official Title
A PHASE I TRIAL OF BUTYRATE AND GANCICLOVIR IN EBV-ASSOCIATED MALIGNANCIES
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
December 1994 (undefined)
Primary Completion Date
July 2000 (Actual)
Study Completion Date
July 2000 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Boston Medical Center

4. Oversight

5. Study Description

Brief Summary
RATIONALE: The Epstein Barr virus can cause cancer and lymphoproliferative disorders. Ganciclovir is an antiviral drug that acts against the Epstein Barr virus. Arginine butyrate may make virus cells more sensitive to ganciclovir. Combining ganciclovir and arginine butyrate may kill more Epstein Barr virus cells and tumor cells. PURPOSE: Phase I trial to study the effectiveness of arginine butyrate plus ganciclovir in treating patients who have cancer or lymphoproliferative disorders that are associated with the Epstein Barr virus.
Detailed Description
OBJECTIVES: Determine the safety, toxicity, and the reversibility of toxicity of arginine butyrate in patients with Epstein Barr virus-induced malignancies or lymphoproliferative disorders. Determine the clinical pharmacology of arginine butyrate when administered with ganciclovir, including plasma half life and major routes of elimination in these patients. Determine the biologic effects of arginine butyrate in terms of inducing sensitivity to ganciclovir in tissue samples from selected patients. Determine the antitumor activity of this treatment regimen in these patients. OUTLINE: Patients receive ganciclovir IV over 1 hour twice a day on days -1 to 21 for the first course (days 0-21 for all subsequent courses) and escalating doses of arginine butyrate IV continuously on days 0-21. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed for a minimum of 42 days. PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Precancerous Condition, Small Intestine Cancer
Keywords
stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, small intestine lymphoma, childhood immunoblastic large cell lymphoma, grade I lymphomatoid granulomatosis, grade II lymphomatoid granulomatosis, adult grade III lymphomatoid granulomatosis, recurrent adult grade III lymphomatoid granulomatosis, childhood grade III lymphomatoid granulomatosis, recurrent childhood grade III lymphomatoid granulomatosis, recurrent grade I lymphomatoid granulomatosis, recurrent grade II lymphomatoid granulomatosis, stage II childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage I adult Burkitt lymphoma, T-cell large granular lymphocyte leukemia, stage II grade 1 follicular lymphoma, stage II grade 2 follicular lymphoma, stage II grade 3 follicular lymphoma, stage II adult diffuse small cleaved cell lymphoma, stage II adult diffuse mixed cell lymphoma, stage II adult diffuse large cell lymphoma, stage II adult immunoblastic large cell lymphoma, stage II adult lymphoblastic lymphoma, stage II adult Burkitt lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, stage I childhood small noncleaved cell lymphoma, stage I childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood large cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood small noncleaved cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, stage II mantle cell lymphoma, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage I marginal zone lymphoma, stage I small lymphocytic lymphoma, stage II small lymphocytic lymphoma, stage II marginal zone lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
arginine butyrate
Intervention Type
Drug
Intervention Name(s)
ganciclovir

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed malignancy or lymphoproliferative disease including the following: Nasopharyngeal carcinoma Hodgkin's lymphoma African Burkitt's lymphoma T-cell non-Hodgkin's lymphoma B-cell non-Hodgkin's lymphoma if Epstein Barr Virus (EBV) positive Other lymphomas associated with immunodeficiency or immunosuppression, including AIDS-related lymphoma B-cell lymphoproliferative disorders Monoclonal or oligoclonal B-cell lymphoid disease (no polyclonal disease) EBV positive by immunohistochemistry or in situ hybridization Negative serology for EBV allowed PATIENT CHARACTERISTICS: Age: 3 and over Performance status: Any status Hematopoietic: Absolute granulocyte count at least 1,000/mm^3 Platelet count at least 50,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL Aminotransferase less than 2 times normal Renal: Creatinine less than 3.0 mg/dL Creatinine clearance greater than 30 mL/min Cardiovascular: No acute myocardial infarction within the past 6 months No atrial fibrillation within the past 6 months Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Prior bone marrow or stem cell transplantation allowed No concurrent immunotherapy No concurrent interferon or tacrolimus Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered No concurrent cytotoxic chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: Recovered from prior radiotherapy Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas V. Faller, MD, PhD
Organizational Affiliation
Boston Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Methodist Cancer Center at Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Cancer Research Center at Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Hopital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
D-30625
Country
Germany
Facility Name
Istituto Nazionale per lo Studio e la Cura dei Tumori
City
Milan
ZIP/Postal Code
20133
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
11555713
Citation
Faller DV, Mentzer SJ, Perrine SP. Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr Opin Oncol. 2001 Sep;13(5):360-7. doi: 10.1097/00001622-200109000-00008.
Results Reference
background
PubMed Identifier
11493400
Citation
Mentzer SJ, Perrine SP, Faller DV. Epstein--Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. Transpl Infect Dis. 2001 Sep;3(3):177-85. doi: 10.1034/j.1399-3062.2001.003003177.x.
Results Reference
background
PubMed Identifier
17119113
Citation
Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, Fingeroth J, Askin M, Levy A, Mentzer SJ, Di Nicola M, Gianni AM, Klein C, Horwitz S, Faller DV. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007 Mar 15;109(6):2571-8. doi: 10.1182/blood-2006-01-024703. Epub 2006 Nov 21.
Results Reference
result
PubMed Identifier
9628848
Citation
Mentzer SJ, Fingeroth J, Reilly JJ, Perrine SP, Faller DV. Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr-virus-associated lymphoma. Blood Cells Mol Dis. 1998 Jun;24(2):114-23. doi: 10.1006/bcmd.1998.0178.
Results Reference
result

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Ganciclovir Plus Arginine Butyrate in Treating Patients With Cancer or Lymphoproliferative Disorders Associated With the Epstein Barr Virus

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