This pilot phase I trial studies the side effects of atezolizumab, gemcitabine, oxaliplatin, and rituximab and to see how well they work in treating patients with transformed diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving atezolizumab, gemcitabine, oxaliplatin, and rituximab may work better in treating patients with transformed diffuse large B-cell lymphoma.
PRIMARY OBJECTIVES: I. Assess the safety and toxicity of atezolizumab in combination with immunogenic chemotherapy (gemcitabine plus oxaliplatin) with rituximab (R-GEMOX-ATEZO) in patients with relapsed or refractory (rel/ref) transformed diffuse large B-cell lymphoma (DLBCL), including determination of the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of R-GEMOX-ATEZO. II. Evaluate on-treatment changes in density of and proximity between immune cell subsets in the tumor microenvironment after immunogenic chemotherapy alone and R-GEMOX-ATEZO. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Evaluate genomic (e.g. gene expression profiles, whole exome sequencing) characteristics of patients with rel/ref transformed DLBCL treated with R-GEMOX-ATEZO. OUTLINE: INDUCTION PHASE: Patients receive rituximab intravenously (IV), gemcitabine IV, and oxaliplatin IV every 2 weeks. Starting cycle 2, patients also receive atezolizumab IV over 30-60 minutes every 2 weeks. Treatment repeats every 14 days of cycle 1 and every 28 days for up to 4 cycles in the absence of disease progression or unaccepted toxicity. Patients also undergo computed tomography (CT), positron emission tomography (PET)-CT, magnetic resonance imaging (MRI), bone marrow biopsy, collection of blood samples, and tumor biopsy throughout induction phase. MAINTENANCE PHASE: Patients receive rituximab IV and atezolizumab over 30-60 minutes IV on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unaccepted toxicity. Patients also undergo CT, PET-CT, MRI, bone marrow biopsy, and collection of blood samples throughout maintenance phase. After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Given IV
Undergo biopsy
Undergo collection of blood samples
Undergo bone marrow biopsy
Undergo CT or PET-CT
Given IV
Undergo MRI
Given IV
Undergo PET-CT
Given IV
City of Hope Comprehensive Cancer Center
Duarte, California, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Incidence of adverse events
Adverse events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Observed toxicities will be summarized by dose limiting toxicity (DLT) (yes/no) as well as by type (organ affected or laboratory determination such as absolute neutrophil count), severity, cycle experienced, and attribution. All patients who begin treatment will be included in the summaries of toxicity.
Time frame: Up to course 2 (42 days)
Maximum tolerated dose (MTD) and recommended phase 2 dose
MTD and recommended phase 2 dose will be determined by DLT. Toxicities will be graded according to CTCAE criteria version 5.0. The study will use a traditional 3+3 design.
Time frame: Course 2, up to 28 days
Complete response rate
Will be assessed by the 2014 Lugano classification.
Time frame: Up to 1 year
Best overall response rate (complete response + partial response)
Will be assessed by the 2014 Lugano classification. Exact 95% confidence intervals will be calculated for these estimates. Confirmation of progressive disease in patients with indeterminate responses as assessed by the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria will be compared with standard assessment of progressive disease by the 2014 Lugano classification.
Time frame: Up to 1 year
Biomarker analysis
Will assess whole exome sequencing (WES) and gene expression profiling (GEP) and immune cell subset density and relative proximities in the tumor microenvironment. Will also explore associations between these and clinical outcome as measured by response and progression free survival. Initially, visual displays (e.g. scatterplots or Kaplan-Meier plots or contingency tables), as well as point estimates and associated 95% confidence intervals, will used to summarize the baseline levels and associations with outcome.
Time frame: Up to 1 year
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