Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines
Status:
Completed
Trial end date:
2010-03-05
Target enrollment:
Participant gender:
Summary
The idiotype of the immunoglobulin on a given B cell malignancy (Id) can serve as a clonal
marker, and a previous pilot study in lymphoma patients has demonstrated that autologous Id
protein can be formulated into an immunogenic, tumor specific antigen by conjugation to a
carrier protein (KLH) and administration with an emulsion-based adjuvant. The goals of
vaccine development in the current study are to develop vaccines: 1) with improved potency
and 2) which are more effective at inducing cell-mediated immune responses. The selection of
GM-CSF as the immunological "adjuvant" is a direct extension of our laboratory studies in
small animal models demonstrating that GM-CSF can enhance the potency of the prototype Id-KLH
vaccine by augmenting almost exclusively the cellular arm of the immune response.
The objectives of this study are: 1) to evaluate cellular and humoral immune responses
against the unique idiotype of the patient's lymphoma and 2) to evaluate the ability of the
Id vaccine to clear the bone marrow of malignant cells detectable by pathologic examination
or molecular examination (polymerase chain reaction amplification of the rearranged bcl-2
oncogene).
The goal of this study is to treat previously untreated patients with follicular lymphomas to
complete remission or minimal residual disease with ProMACE chemotherapy. Three to six months
after completion of chemotherapy, in an effort to reduce the relapse rate (by eradicating
microscopic disease resistant to chemotherapy), patients will receive an autologous Id
vaccine administered in combination with GM-CSF. Id-KLH (0.5 mg) is administered
subcutaneously. GM-CSF is administered subcutaneously locally with the vaccine on the day of
vaccination and for the three consecutive days following vaccination as close to the initial
vaccination site as possible at one of two doses (patients are randomized to either a high or
low dose, 500 or 100 micrograms/m2).
We plan to accrue 42 patients. Twenty-nine patients have been enrolled. Sixteen patients have
entered and/or completed the vaccination phase. Patients have demonstrated significant
lymphoproliferative responses specific for autologous idiotype of a magnitude which is
significantly greater than previously observed.