tafasitamab + lenalidomide + r-chop versus r-chop in newly diagnosed high-intermediate and high risk dlbcl patients

Conditions: Diffuse Large B-cell Lymphoma

Summary: this is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to compare the efficacy and safety of the humanized monoclonal anti cd19 antibody tafasitamab plus lenalidomide in addition to r-chop (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) versus r-chop in previously untreated, high-intermediate and high-risk patients with newly-diagnosed dlbcl


Eligibility criteria:
major inclusion criteria: * 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: 1. dlbcl, nos including gcb type, abc type 2. t-cell rich large bcl 3. epstein-barr virus-positive dlbcl, nos 4. anaplastic lymphoma kinase (alk)-positive large bcl 5. human herpes virus-8 (hhv8)-positive dlbcl, nos 6. 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 7. hgbl-nos 8. dlbcl coexistent with either follicular lymphoma (fl) of any grade, gastric malt lymphoma or non-gastric malt lymphoma 9. 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 major exclusion criteria: * 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: 1. malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening 2. adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer 3. 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

Keywords: dlbcl cd19 monoclonal antibody tafasitamab lenalidomide r-chop diffuse large b-cell lymphoma