Atezolizumab, Gemcitabine, Oxaliplatin, and Rituximab in Treating Patients With Relapsed or Refractory Transformed Diffuse Large B-Cell Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03321643|
Recruitment Status : Recruiting
First Posted : October 26, 2017
Last Update Posted : May 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Diffuse Large B-Cell Lymphoma Recurrent Transformed Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Transformed Non-Hodgkin Lymphoma Richter Syndrome Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma||Drug: Atezolizumab Drug: Gemcitabine Other: Laboratory Biomarker Analysis Drug: Oxaliplatin Biological: Rituximab||Phase 1|
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 by multispectral immunofluorescence, including density of CD8+ cells and cytotoxic lymphocyte (CTL):regulatory T cell (Treg) ratio.
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.
INDUCTION PHASE: Patients receive rituximab intravenously (IV), gemcitabine IV, and oxaliplatin IV every 2 weeks. Starting course 2, patients also receive atezolizumab IV over 30-60 minutes every 2 weeks. Treatment repeats every 14 days of course 1 and every 28 days for up to 4 courses in the absence of disease progression or unaccepted toxicity.
MAINTENANCE PHASE: Patients receive rituximab IV and atezolizumab over 30-60 minutes IV on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unaccepted toxicity.
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 (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Phase I Study of Atezolizumab (MPDL3280A) in Combination With Immunogenic Chemotherapy (Gemcitabine-Oxaliplatin) and Rituximab for Transformed Diffuse Large B-Cell Lymphoma|
|Actual Study Start Date :||March 7, 2018|
|Estimated Primary Completion Date :||June 30, 2021|
|Estimated Study Completion Date :||June 30, 2021|
Experimental: Treatment (rituximab, gemcitabine, oxaliplatin, atezolizumab)
INDUCTION PHASE: Patients receive rituximab IV, gemcitabine IV, and oxaliplatin IV every 2 weeks. Starting course 2, patients also receive atezolizumab IV over 30-60 minutes every 2 weeks. Treatment repeats every 14 days of course 1 and every 28 days for up to 4 courses in the absence of disease progression or unaccepted toxicity.
MAINTENANCE PHASE: Patients receive rituximab IV and atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unaccepted toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of adverse events [ Time Frame: Up to course 2 (42 days) ]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.
- Maximum tolerated dose (MTD) and recommended phase 2 dose [ Time Frame: Course 2, up to 28 days ]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.
- Complete response rate [ Time Frame: Up to 1 year ]Will be assessed by the 2014 Lugano classification.
- Best overall response rate (complete response + partial response) [ Time Frame: Up to 1 year ]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) criteria35 will be compared with standard assessment of progressive disease by the 2014 Lugano classification.
- Biomarker analysis [ Time Frame: Up to 1 year ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03321643
|United States, California|
|City of Hope Comprehensive Cancer Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Site Public Contact 800-826-4673 firstname.lastname@example.org|
|Principal Investigator: Alex F. Herrera|
|UC San Diego Moores Cancer Center||Recruiting|
|La Jolla, California, United States, 92093|
|Contact: Site Public Contact 858-822-5354 email@example.com|
|Principal Investigator: Carolyn M. Mulroney|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Site Public Contact 916-734-3089|
|Principal Investigator: Joseph M. Tuscano|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Site Public Contact 404-778-1868|
|Principal Investigator: Pamela B. Allen|
|Principal Investigator:||Alex F Herrera||City of Hope Comprehensive Cancer Center LAO|