This single-arm, interventional phase 2 study is designed to evaluate whether the inclusion of mosunetuzumab subcutaneous and polatuzumab vedotin (Mosun-Pola) to a split-dose CHP chemotherapy backbone will improve outcomes for elderly patients with a new diagnosis of diffuse large B-cell lymphoma.
Patients aged 70-74 who are determined to be unfit or frail by the Cumulative Illness Rating Scale-Geriatric (CIRS-G) score with 5-8 comorbid conditions scored 2 or more than 1 comorbidity scored 3-4 are allowed.
Newly diagnosed, untreated, biopsy-proven CD20 positive diffuse large B-cell lymphoma (DLBCL) (including high-grade B-cell lymphoma and T-cell/histiocyte-rich large B-cell lymphoma). Patients with discordant bone marrow (i.e., involved by low-grade/indolent non-Hodgkin lymphoma) are eligible. Patients with transformed DLBCL from underlying low-grade disease are eligible. Patients with composite DLBCL and concurrent low-grade lymphoma are eligible. Patients with prior treatment for low-grade NHL with non-anthracycline based regimens are eligible.
Measurable disease by positron emission tomography (PET) / computed tomography (CT) using the Lugano criteria (lymph node >1.5 cm or extranodal site >1.0 cm).
Adequate biospecimen sample that meets current Adaptive Clonality ID Test specimen requirements for DLBCL.
Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy.
Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease.
Prior allogeneic or autologous stem cell transplant.
Prior solid organ transplant.
Single group
Polatuzumab Vedotin
DrugA combination of a monoclonal antibody and a chemotherapy drug.
Mosunetuzumab
DrugA monoclonal antibody.
Cyclophosphamide
DrugChemotherapy drug, alkylating agent.
Doxorubicin
DrugChemotherapy drug, anthracycline antibiotic.
Prednisone
DrugSteroid, anti-inflammatory
Pegfilgrastim
Other interventionGranulocyte stimulating factor, biologic response modifier.
Complete Response
This is defined as the number of subjects achieving a complete response at the end of treatment using the Lugano criteria.
Partial Response
This is defined as the number of subjects achieving a partial response at the end of treatment using the Lugano criteria.
Duration of Response
This is defined as the time from the first documentation of tumor response to disease progression (per the Lugano criteria), relapse, or death among patients who achieve a response of partial response or better. The measure will be the median duration of response in months.
Overall Survival
This outcome measure is the number of subjects expiring from any cause.
Adverse Events
The number of grade 3 or higher adverse events possibly, probably, or definitely related to study therapy in the safety run-in population from the start of therapy through 30 days after the end of study therapy. Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded using the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system described by Lee et al., 2019. The scale for ICANS will be the ASTCT ICANS consensus grading for adults. The score evaluates neurotoxicity domains. The lowest grade is 1 (less severe) and the highest is 4 (more severe). The ASTCT Consensus Grading for CRS, is based on the severity of the patient's symptoms. The lowest grade is 1 and the highest is 4. The higher the grade, the more severe.
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