Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines
Id-KLH Vaccine
+ GM-CSF
Maladies hématologiques et lymphatiques+8
+ Maladies du Système Immunitaire
+ Troubles immunoprolifératifs
Étude thérapeutique
Résumé
Date de début de l'étude : 9 septembre 1996
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.42 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
INCLUSION CRITERIA: Patients must meet all of the following eligibility criteria. Tissue diagnosis of: follicular small cleaved cell, or follicular mixed lymphoma with surface IgM, IgG or IgA phenotype with a monoclonal heavy and light chain. Pathology slides must be submitted to the NIH Pathology Department for review. Stage III or IV lymphoma. Only previously untreated patients are eligible. Previous treatment with radiation alone (less than TBI) is permissible. A single peripheral lymph node of at least 2 cm size accessible for biopsy/harvest. Karnofsky status greater than or equal to 70 percent. Life expectancy of greater than 1 year. Serum creatinine less than or equal to 1.5 mg per dl unless felt to be secondary to lymphoma. Bilirubin less than or equal to 1.5 mg/dl unless felt to be secondary to lymphoma or Gilbert's disease. SGOT/SGPT less than or equal to 3.5 times upper limit of normal. Ability to give informed consent. Ability to return to clinic for adequate follow-up for the period that the protocol requires. EXCLUSION CRITERIA: Prior total body irradiation. Presence of antibodies to HIV, hepatitis B surface antigen or other active infectious process. Pregnancy or lactation. Fertile men and women must plan to use effective contraception. A beta-HCG level will be obtained in women of child-bearing potential. Patients with previous or concomitant malignancy, regardless of site, except curatively treated squamous or basal cell carcinoma of the skin, or effectively treated carcinoma in situ of the cervix. Patients unwilling to give informed consent. Failure to meet any of the inclusion criteria. Any medical or psychiatric condition that in the opinion of the protocol chairman would compromise the patient's ability to tolerate this treatment will be excluded from this protocol. Patient with CNS lymphoma (current or previously treated) will not be eligible.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, United StatesOuvrir National Institutes of Health Clinical Center, 9000 Rockville Pike dans Google Maps