Resumen

Este es un ensayo de fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo diseñado para comparar la eficacia y seguridad del anticuerpo monoclonal humanizado anti-CD19 tafasitamab más lenalidomida además de R-CHOP (rituximab, ciclofosfamida, doxorrubicina, vincristina y prednisona) versus R-CHOP en pacientes con LDCBG de nuevo diagnóstico, de riesgo intermedio-alto y alto, sin tratamiento previo.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 80 YearsSexo: ALL

Criterios de inclusión

Previously untreated patients with local biopsy-proven, CD20-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms are eligible:
DLBCL, NOS including GCB type, ABC type
T-cell rich large BCL
Epstein-Barr virus-positive DLBCL, NOS
Anaplastic lymphoma kinase (ALK)-positive large BCL
Human herpes virus-8 (HHV8)-positive DLBCL, NOS
High-grade BCL with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma). Please note: Patients must be appropriate candidates for R-CHOP. If an investigator deems a patient with a known double- or triple-hit lymphoma (HGBL) should be treated more aggressively (e.g. dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab \[DA-EPOCH-R\] or cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) followed by methotrexate and cytarabine \[Hyper CVAD\]), this patient would not be considered eligible for this study
HGBL-NOS
DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT lymphoma or non-gastric MALT lymphoma
FL grade 3b
Availability of archival or freshly collected tumor tissue sent for retrospective central pathology review
IPI status of 3 to 5 (for patients \> 60 years of age) or aaIPI 2 to 3 (for patients ≤ 60 years of age)
Diagnosis to treatment interval, defined as the time between the date of DLBCL diagnosis (date of the first biopsy specimen containing B Cell lymphoma according to the local pathology report) and the start of treatment (C1D1) ≤ 28 days
ECOG performance status of 0, 1, or 2
Left ventricular ejection fraction equal to or greater 50% as assessed by local echocardiography or cardiac multi-gated acquisition (MUGA) scan
Adequate hematologic function
Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from breast feeding and donating eggs; agreement to ongoing pregnancy testing during the course of the study, and after study therapy has ended
Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm

Criterios de exclusión

Any other histological type of lymphoma according to WHO 2016 classification of lymphoid neoplasms, e.g., primary mediastinal (thymic) large B-cell lymphoma, Burkitt's lymphoma, BCL, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (grey-zone lymphoma); primary effusion lymphoma; primary cutaneous DLBCL, leg type; primary DLBCL of the CNS; DLBCL arising from CLL or indolent lymphoma
History of prior non-hematologic malignancy except for the following:
Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening
Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer
Adequately treated carcinoma in situ without current evidence of disease
Any systemic anti-lymphoma and/or investigational therapy prior to the start of C1D1, except for permitted pre-phase treatment
Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines
Known CNS lymphoma involvement
Known active systemic bacterial, viral, fungal, or other infection at screening, including patients with suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay)
History or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that in the investigator's opinion would preclude participation in the study or compromise the patient's ability to give informed consent

Intervenciones

drug

Tafasitamab

Tafasitamab IV infusion will be administered as per the schedule specified in the respective arm.

drug

Lenalidomide

Lenalidomide PO will be administered as per the schedule specified in the respective arm.

drug

Rituximab

Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

drug

Cyclophosphamide

Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

drug

Doxorubicin

Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

drug

Vincristine

Vincristine IV infusion will be administered as per the schedule specified in the respective arm.

drug

Prednisone

Prednisone PO will be administered as per the schedule specified in the respective arm.

drug

Tafasitamab placebo

0.9% saline solution IV infusion will be administered as per the schedule specified in the respective arm.

drug

Lenalidomide placebo

Placebo matching to lenalidomide PO will be administered as per the schedule specified in the respective arm.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Tafasitamab

Lenalidomide

Rituximab

Cyclophosphamide

Doxorubicin

Vincristine

Prednisone

Tafasitamab placebo

Lenalidomide placebo

Ubicaciones

MorphoSys Research Site

MorphoSys Research Site

MorphoSys Research Site

MorphoSys Research Site

MorphoSys Research Site

Patrocinadores