Clinical trial NCT00006340: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Paris
country: France
facility: Hopital Necker
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Milan
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
Study officials:
affiliation: Boston Medical Center
name: Douglas V. Faller, MD, PhD
role: STUDY_CHAIR
References:
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.
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.
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.
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.