The purpose of this research study is to test if a combination treatment of chimeric antigen receptor (CAR) T-cell therapy, Mosunetuzumab, and Polatuzumab Vedotin will result in tumor reduction.
Diffuse large B cell lymphoma (DLBCL) not otherwise specified. Patients with primary cutaneous DLBCL of leg-type are eligible if the lymphoma expresses cluster of differentiation 19 (CD19) and if the insurance approves the CAR-T therapy. Similarly. Large cell transformation of nodal or extra-nodal marginal zone lymphoma is eligible only if the insurance allows and the disease shows strong CD19 positivity. On the other hand, post-transplant lymphoproliferative disorders (PTLD) are not allowed due to the frequently required continuation of immunosuppression to avoid organ rejection.
Primary mediastinal B cell lymphoma (PMBCL)
Transformed follicular lymphoma (TFL). An untransformed follicular lymphoma grade 3B will be considered on a case by case basis, since the genetic signature of grade 3B follicular lymphoma frequently resemble that of DLBCL and the large lymphomatous cells just happen to be organized in a follicular pattern. Recently, Breyanzi has an FDA indication for follicular lymphoma grade 3B.
High grade B cell lymphoma (HGBL), other than B-lymphoblastic lymphoma
Patients with EBV+DLBCL, plasmablastic lymphoma, human herpesvirus-8 (HHV-8) related B cell lymphoproliferative disorders including primary effusion lymphoma, anaplastic lymphoma kinase (ALK)+ LBCL, intravascular large B cell lymphomas, DLBCL associated with chronic inflammation, lymphomatoid granulomatosis, primary DLBCL of the CNS and T cell histiocyte rich LBCL will not be allowed because of different biology, frequent lack of CD19, difficulty in interpreting toxicity (as in the case of primary central nervous system (CNS) lymphoma) or some preliminary discouraging results with CAR-T as in the case of T-cell, histiocyte-rich large B cell lymphoma and Richter transformation of chronic lymphocytic leukemia (CLL).
Primary CNS lymphoma or secondary CNS involvement by lymphoma.
Similarly, patients with conditions that increase the risk of CNS toxicity will be excluded. Such conditions include but not limited to
active seizure disorder for which an antiepileptic is taken,
Single group
Mosunetuzumab
DrugInduction Phase (Days -42 through -7): * 1 mg of Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -42. * 2 mg of Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -35. * 60 mg of Mosunetuzumab administered via intravenous (IV) infusion on (given as per treatment guidelines) on Days -28 and -7. Consolidation Phase (Day +1 through Day +90): 30 mg IV Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Days +14, +35, +56 and +77.
Polatuzumab
DrugInduction Phase (Days -42 through -7): 1.8mg/kg of Polatuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -28. Consolidation Phase (Days +1 through +90): 1.8mg/kg of Polatuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Days +35, +56 and +77.
CAR-T Cell Therapy
Biological/VaccineParticipants will receive CAR-T Cell therapy via infusion on Day 0 (given as per treatment guidelines). Prior to CAR-T Cell Therapy, participants will begin receiving lymphodepleting chemotherapy on Days -5 through -3 (given as per treatment guidelines).
Complete Response Rate
Complete Response (CR) rate will be reported as the percentage of participants achieving complete response (CR) to study treatment. Response to therapy will be assessed using Positron Emission Tomography (PET)/ Computerized Tomography (CT) scan following Lugano 2014 criteria (Cheson et al, Journal of Clinical Oncology (JCO), 2014) at 3 months (Day +90) of study treatment. For equivocal PET-CT results, biopsy will be performed after day +90 PET/CT to assess true CR or persistent lymphoma.
Overall Response Rate (ORR)
Overall response rate (ORR) will be reported as the percentage of participants achieving either complete response (CR) or partial response (ORR = CR + PR) to study treatment. Response to therapy will be assessed using Positron Emission Tomography (PET)/ Computerized Tomography (CT) scan following Lugano 2014 criteria (Cheson et al, Journal of Clinical Oncology (JCO), 2014) up to Day +90 of study treatment.
Progression free survival (PFS) Rate
PFS is defined as the elapsed time from the date of starting treatment to the date of progression, or date of death from any cause; whichever comes first. PFS rate will be reported as the percentage of participants without progressive disease after start of treatment.
Overall Survival (OS) Rate
Overall survival is defined as the elapsed time from the date of starting treatment to the date of death from any cause. OS rate will be reported as the percentage of participants still alive after start of treatment.
Minimal residual disease (MRD) negativity
Minimal residual disease (MRD) negativity will be reported as the percentage of participants showing absence of measurable disease in peripheral blood after start of CAR-T Cell therapy. MRD negativity will be assessed by using the Clustering and Alignment of Polymorphic Sequences (CAPSeq) assay.
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