Vaccine Therapy in Treating Patients With Lymphoplasmacytic Lymphoma

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of using a novel lymphoma deoxyribonucleic acid
(DNA) vaccine encoding macrophage inflammatory protein 3 alpha (MIP3a)-fused lymphoma
idiotype in single chain format.

II. To determine the maximum tolerated dose (MTD) of the vaccine.

SECONDARY OBJECTIVES:

I. To assess the immunogenicity of the vaccine to generate tumor-specific cellular and
humoral immune responses.

OUTLINE: This is a dose-escalation study.

Patients receive autologous lymphoma immunoglobulin-derived single-chain variable fragment
(scFV)-chemokine DNA vaccine intradermally (ID) at 0, 4, and 8 weeks.

After completion of study treatment, patients are followed up at 4 weeks, and then every 6
months for 1 year.

Inclusion Criteria:

- Tissue diagnosis of lymphoplasmacytic lymphoma with surface immunoglobulin G (IgG),
immunoglobulin A (IgA) or immunoglobulin M (IgM) phenotype with a monoclonal heavy and
light chain as determined by flow cytometry; all primary diagnostic lymph node and/or
bone marrow biopsies will be reviewed at the University of Texas M.D. Anderson Cancer
Center (UTMDACC)

- Previously untreated patients with lymphoplasmacytic lymphoma (of any subtype: IgG,
IgA, IgM) in the asymptomatic phase

- Patients must provide a lymph node sample of at least 1.5 cm in the long axis, or a
bone marrow aspiration sample providing at least 5 million cluster of differentiation
(CD)20 and/or CD38+ (approximately 10 ml)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Serum creatinine =< 1.5 mg/dl and a creatinine clearance >= 30 ml/min

- Total bilirubin =< 1.5 mg/dl unless felt secondary to Gilbert's disease

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 x upper limit of
normal

- Ability to provide informed consent, and to return to clinic for adequate follow-up
for the period that the protocol requires

- Female subject is either post-menopausal or surgically sterilized or willing to use an
acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study and for 30 days after the last vaccination has been administered

- Male subject agrees to use an acceptable method for contraception for the duration of
the study

Exclusion Criteria:

- Human immunodeficiency virus (HIV), hepatitis B and/or hepatitis C infection

- Pregnancy or lactating females

- Patients with previous history of malignancy within the last 5 years except curatively
treated squamous or basal cell carcinoma of the skin or curatively treated carcinoma
in-situ of other organs

- Any medical or psychiatric condition that in the opinion of the principal investigator
would compromise the patient's ability to tolerate this treatment

- Patients with New York Heart Association class 3 or 4 disease

- Patients with a history of autoimmune diseases except for Hashimoto's thyroiditis

- Patients with positive antinuclear antibody (ANA) and/or anti-double strand (ds) DNA
antibodies