Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	3 and over	Other	BUMC-3756 BUSM-FDR001532, NCI-V00-1609, NCT00006340

Objectives

1. Determine the safety, toxicity, and the reversibility of toxicity of arginine butyrate in patients with Epstein Barr virus-induced malignancies or lymphoproliferative disorders.
2. Determine the clinical pharmacology of arginine butyrate when administered with ganciclovir, including plasma half life and major routes of elimination in these patients.
3. Determine the biologic effects of arginine butyrate in terms of inducing sensitivity to ganciclovir in tissue samples from selected patients.
4. Determine the antitumor activity of this treatment regimen in these patients.

Entry 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

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

Patient Characteristics:

Age:

• 3 and over

Performance status:

• Any status

Hematopoietic:

• Absolute granulocyte count at least 1,000/mm³
• Platelet count at least 50,000/mm³

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

Expected Enrollment

Approximately 20 patients will be accrued for this study within 2 years.

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.

Perrine SP, Hermine O, Small T, et al.: A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 109 (6): 2571-8, 2007.[PUBMED Abstract]

Mentzer SJ, Fingeroth J, Reilly JJ, et al.: Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr-virus-associated lymphoma. Blood Cells Mol Dis 24 (2): 114-23, 1998.[PUBMED Abstract]

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 13 (5): 360-7, 2001.[PUBMED Abstract]

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 3 (3): 177-85, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Boston University Cancer Research Center

Douglas Faller, MD, PhD, Protocol chair		Ph: 617-638-4173

Registry Information
Official Title		A PHASE I TRIAL OF BUTYRATE AND GANCICLOVIR IN EBV-ASSOCIATED MALIGNANCIES
Trial Start Date		1994-12-15
Registered in ClinicalTrials.gov		NCT00006340
Date Submitted to PDQ		1994-12-15
Information Last Verified		2004-11-22

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