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

Lymphoma Clinical Trial

Official title:

A PHASE I TRIAL OF BUTYRATE AND GANCICLOVIR IN EBV-ASSOCIATED MALIGNANCIES

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006340
• Other study ID #: CDR0000064947
• Secondary ID: BUMC-3756BUSM-FD
• Status: Completed
• Phase: Phase 1
• First received: October 4, 2000
• Last updated: July 25, 2013
• Start date: December 1994
• Est. completion date: July 2000

Study information

• Verified date: July 2013
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: July 2000
• Est. primary completion date: July 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Lymphoproliferative Disorders
• Precancerous Condition
• Precancerous Conditions
• Small Intestine Cancer

Intervention

Drug:
• arginine butyrate

• ganciclovir

Locations

Country	Name	City	State
France	Hopital Necker	Paris
Germany	Medizinische Hochschule Hannover	Hannover
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Milan
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Boston Medical Center

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy, 

References & Publications (4)

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. Review. — View 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. — View 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. Review. — View 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-ass — View Citation