Una nueva vacuna (EO2463) como monoterapia y en combinación, para el tratamiento de pacientes con linfoma no Hodgkin indolente (SIDNEY)
Un ensayo global multicéntrico de fase 1/2 de EO2463, una nueva vacuna terapéutica peptídica derivada de microbios, como monoterapia y en combinación con lenalidomida y rituximab, para el tratamiento de pacientes con linfoma no Hodgkin indolente
The purpose of this study is to define the recommended Phase 2 Dose, safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 during monotherapy and in combination with lenalidomide and/or rituximab in patients with indolent NHL
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
EO2463 Is an innovative cancer peptide therapeutic vaccine based on the homologies between tumor associated antigens and microbiome-derived peptides that will be administered alone and in combination with lenalidomide, rituximab, and lenalidomide/rituximab to generate safety and preliminary efficacy data in patients with indolent NHL
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Barcelona, España
- University Hospital Vall d'Hebron, Institute of Oncology
-
Madrid, España
- Clinica Universidad de Navarra
-
Pamplona, España
- Clinica Universidad de Navarra
-
Salamanca, España
- Hospital Clinico Universitario de Salamanca
-
-
-
-
Massachusetts
-
Boston, Massachusetts, Estados Unidos, 02215
- Dana Farber Cancer Institute
-
-
Minnesota
-
Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
-
-
New York
-
Rochester, New York, Estados Unidos, 14642
- University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)
-
-
Washington
-
Seattle, Washington, Estados Unidos, 98109
- University of Washington-Seattle Cancer Care Alliance
-
-
-
-
-
Amiens, Francia
- CHU d'Amiens-Picardie - Hopital SUD
-
-
-
-
-
Naples, Italia
- IRCCS Policlinico San Matteo Foundation - University of Pavia
-
Pavia, Italia
- IRCCS Policlinico San Matteo Foundation - University of Pavia
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- For inclusion in Cohorts 1 and 4 patients should have relapsed/refractory, biopsy-proven grade 1, 2 or 3A, FL or MZL, ECOG performance status 0 to 2, and have received at least one prior line of treatment. For inclusion in Cohort 4b the above applies except that patients with FL, and not patients with MZL, will be eligible for enrollment.
- For inclusion in Cohort 2 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, low tumor burden by Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, and not be in need of standard of care therapy according to the assessment of the treating physician.
- For inclusion in Cohort 3 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, low tumor burden by GELF criteria and be in need of therapy according to the assessment of the treating physician.
- Patients with an age ≥ 18 years old.
- Patients who are human leukocyte antigen (HLA)-A2 positive.
- Patients should have radiologically measurable disease with a lymph node or tumor mass greater than or equal to 1.5 cm in at least one dimension.
- Males or non-pregnant, non-lactating, females.
- Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
- Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.
Exclusion Criteria:
- Patients treated with dexamethasone > 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2463 administration, unless required to treat an adverse event.
- Patients with grade 3B FL or transformation to an aggressive lymphoma subtype.
- Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment).
- Patients with prior exposure to EO2463.
- Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2463 administration.
- Patients to be included in Cohorts 1 and 4, and who have received rituximab or other B cell ablation therapy within 8 weeks of start of study treatment.
- Patients to be included in Cohorts 4, who received prior CAR T-cell therapy and progressed within 6 months after this therapy.
- Patients with abnormal laboratory values.
- Patients with persistent Grade 3 or 4 toxicities.
- Uncontrolled central nervous system (CNS) metastasis.
- Other malignancy or prior malignancy with a disease-free interval of less than 3 years.
- Patients with clinically significant disease.
- Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).
- Patients with history of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Pregnant and breastfeeding patients.
- Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Cohort 1
Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 monotherapy for 6 weeks followed by addition of lenalidomide. Then, if applicable rituximab (depending on response with EO2463 + lenalidomide) will be added. Four to 18 previously treated patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) were anticipated to be included based on safety findings. |
Multiple dose of EO2463 D1-21 of 4-weekly cycles
Otros nombres:
Multiple doses of rituximab
Otros nombres:
|
|
Experimental: Cohort 2
Anticipated approximatively 25 previously untreated patients with FL or MZL with an evaluation of EO2463 monotherapy (at the established dose in Cohort 1). |
Multiple dose of EO2463 |
|
Experimental: Cohort 3
Anticipated approximatively 6 previously untreated patients with FL or MZL with an evaluation of EO2463 (at the established dose in cohort 1) as monotherapy for 6 weeks followed by addition of rituximab if applicable (depending on response with EO2463 monotherapy). |
Multiple dose of EO2463 Multiple doses of rituximab
Otros nombres:
|
|
Experimental: Cohort 4
Anticipated approximatively 40 patients previously treated patients with FL (or MZL). Evaluation of EO2463 (at the established dose in Cohort 1) in combination with lenalidomide from day 1 and then with addition of rituximab. |
Multiple dose of EO2463 D1-21 of 4-weekly cycles
Otros nombres:
Multiple doses of rituximab
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment |
Periodo de tiempo: Up to 24 months
|
Incidences of adverse events, Treatment-Emergent Adverse events, Serious Adverse Events, Deaths, and Laboratory Abnormalities Using the National Cancer Institute-Common Terminology Criteria for Adverse events (NCI-CTCAE) V5.0. |
Up to 24 months
|
|
Phase 2: Overall Response Rate
Periodo de tiempo: Up to 24 months
|
Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy |
Up to 24 months
|
|
Phase 2: Complete Response Rate
Periodo de tiempo: Up to 24 months
|
Complete remission (CR)-rate according to the Lugano Classification 2014 during therapy with the combination of EO2463/lenalidomide/rituximab. |
Up to 24 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463
Periodo de tiempo: Up to 24 months
|
Immunogenicity will be assessed by interferon-Gamma (IFN-Γ) enzyme-Linked immunospot , and/or by intracellular cytokines staining, and/or multimers staining assays. |
Up to 24 months
|
|
Evaluation of Overall Survival
Periodo de tiempo: Up to 7 years after last patient enrolled
|
The time interval from the date of first study treatment administration to the date of death due to any cause |
Up to 7 years after last patient enrolled
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Jan Fagerberg, MD, Enterome
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Enfermedades linfáticas
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Linfoma No Hodgkin
- Linfoma de células B
- Linfoma
- Enfermedades hemic y linfáticas
- Linfoma Folicular
- Linfoma, Células B, Zona Marginal
- Aminoácidos, péptidos y proteínas
- Proteínas
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Ácidos carboxílicos
- Piperidinas
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Anticuerpos, monoclonales, derivados de murino
- Ftalimidas
- Ácidos ftálicos
- Ácidos, carbocíclicos
- Piperidonas
- Isoindoles
- Lenalidomida
- Rituximab
Otros números de identificación del estudio
- EONHL1-20
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .