Clinical trial NCT01209871: Vaccine Therapy in Treating Patients With Lymphoplasmacytic Lymphoma
Official title: Phase I Study of an Active Immunotherapy for Asymptomatic Phase Lymphoplasmacytic Lymphoma With DNA Vaccines Encoding Antigen-Chemokine Fusion
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lymphoplasmacytic Lymphoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-09-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial studies the side effects and best dose of vaccine therapy in treating patients with lymphoplasmacytic lymphoma. Vaccines made from a person's cancer cells may help the body build an effective immune response to kill cancer cells.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity according to the National Cancer Institute Common Toxicity Criteria version 4.0
timeFrame: 4 weeks
Secondary outcomes:
measure: Immune response defined as at least a three-fold rise in the precursor frequency of tumor-reactive T cells
timeFrame: At 12 weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Sheeba Thomas
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thomas SK, Cha SC, Smith DL, Kim KH, Parshottam SR, Rao S, Popescu M, Lee VY, Neelapu SS, Kwak LW. Phase I study of an active immunotherapy for asymptomatic phase Lymphoplasmacytic lymphoma with DNA vaccines encoding antigen-chemokine fusion: study protocol. BMC Cancer. 2018 Feb 13;18(1):187. doi: 10.1186/s12885-018-4094-2.