Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Projected Accrual
Outline
Published Results
Trial Contact 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 Active 3 and over Other BUMC-3756 BUSM-FDR001532, NCI-V00-1609

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

Projected Accrual

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.

Disclaimer

The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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]

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]

Trial Contact Information

Trial Lead Organizations

Cancer Research Center at Boston Medical Center

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

U.S.A.
Indiana
	Indianapolis
	Methodist Cancer Center at Methodist Hospital
		Michael Ray Niemeier, MD	Ph:  317-929-5820 800-265-3220
Massachusetts
	Boston
	Cancer Research Center at Boston Medical Center
		Douglas Faller, MD, PhD	Ph:  617-638-4173
		Susan Park Perrine, MD	Ph:  617-638-5639
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Steven Horwitz, MD	Ph:  212-639-8889
		Trudy Small, MD	Ph:  212-639-5965
France
	Paris
	Hopital Necker
		Olivier Hermine	Ph:  33-1-44-381-742
Germany
	Hannover
	Medizinische Hochschule Hannover
		Christoph Klein, MD, PhD	Ph:  49-511-532-6710
Italy
	Milan
	Istituto Nazionale per lo Studio e la Cura dei Tumori
		Alessandro M. Gianni, MD	Ph:  39-02-239-0761
		Massimo Di Nicola, MD	Ph:  39-02-239-0761

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