a study to evaluate the safety and efficacy of glofitamab in combination with rituximab (r) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (chop) in circulating tumor (ct)dna high-risk patients with untreated diffuse large b-cell lymphoma

Conditions: Lymphoma

Summary: this phase ii, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (r-chop) in individuals with circulating tumor dna (ctdna) high-risk diffuse large b-cell lymphoma (dlbcl), as the first line of treatment.


Eligibility criteria:
inclusion criteria: * previously untreated patients with cd20-positive dlbcl, including one of the following diagnoses made according to the 2016 world health organization (who) classification of lymphoid neoplasms * dlbcl, not otherwise specified, including gcb and abc/non-gcb types as well as double-expressor lymphoma (coexpression of myc and bcl2) * high-grade b-cell lymphoma (hgbcl) with myc and bcl2 and/or bcl6 translocations * patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the medical monitor * eastern cooperative oncology group (ecog) performance status of 0-2 * international prognostic index (ipi): 2-5 * life expectancy of at least 6 months * adequate biomarker blood samples prior to initiation of r-chop on day 1 of cycle 1 and on day 1 of cycle 2 submitted for screening for determination of ctdna status * at least one bi-dimensionally fluorodeoxyglucose (fdg)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (pet/ct) scan * left ventricular ejection fraction (lvef) \>=50%, as determined on cardiac multiple-gated acquisition (muga) scan or cardiac echocardiogram (echo) * adequate hematopoietic function * contraception use additional inclusion criterion for ctdna high-risk participants: * plasma sample evaluated to be ctdna high risk exclusion criteria: * current diagnosis of b-cell lymphoma, unclassifiable, with features intermediate between dlbcl and classic hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large b-cell lymphoma, t-cell/histiocyte-rich large b-cell lymphoma, burkitt lymphoma, central nervous system (cns) lymphoma (primary or secondary involvement), primary effusion dlbcl, and primary cutaneous dlbcl * contraindication to any of the individual components of r-chop, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products * prior treatment for indolent lymphoma * prior solid organ or allogeneic stem cell transplant * prior therapy for dlbcl and high-grade b-cell lymphoma (hgbcl) with the exception of palliative, short-term treatment with corticosteroids * pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of r-chop, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab