Testing the Addition of an Immunotherapy Agent, Atezolizumab, When Given With the Usual Chemo-Immunotherapy Drug Combination (Rituximab Plus Gemcitabine and Oxaliplatin) for Relapsed/Refractory (That Has Come Back or Not Responded to Treatment) Transformed Diffuse Large B-Cell Lymphoma
A Pilot Phase I Study of Atezolizumab (MPDL3280A) in Combination With Immunogenic Chemotherapy (Gemcitabine-Oxaliplatin) and Rituximab for Transformed Diffuse Large B-Cell Lymphoma
4 other identifiers
interventional
24
1 country
4
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2018
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 25, 2017
CompletedFirst Posted
Study publicly available on registry
October 26, 2017
CompletedStudy Start
First participant enrolled
September 18, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
April 13, 2026
December 1, 2025
7.8 years
October 25, 2017
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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.
Course 2, up to 28 days
Secondary Outcomes (3)
Complete response rate
Up to 1 year
Best overall response rate (complete response + partial response)
Up to 1 year
Biomarker analysis
Up to 1 year
Study Arms (1)
Treatment (rituximab, gemcitabine, oxaliplatin, atezolizumab)
EXPERIMENTALINDUCTION PHASE: Patients receive rituximab 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 CT, PET-CT, MRI, bone marrow biopsy, collection of blood samples, and tumor biopsy throughout induction phase. MAINTENANCE PHASE: Patients receive rituximab IV and atezolizumab IV over 30-60 minutes 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.
Interventions
Undergo CT or PET-CT
Given IV
Undergo MRI
Given IV
Given IV
Given IV
Undergo biopsy
Undergo collection of blood samples
Undergo bone marrow biopsy
Undergo PET-CT
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed transformed diffuse large B-cell lymphoma (DLBCL), including histologic transformation from any indolent lymphoma (e.g. follicular or marginal zone lymphoma) or Richter transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
- Patients must have measurable disease by CT or PET scan, with one or more sites of disease \>= 1.5 cm in longest dimension
- Relapsed or refractory disease after at least 1 prior regimen, defined using the 2014 Lugano classification
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of atezolizumab in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 3 months
- Leukocytes \>= 2,500/mcL, unless documented bone marrow involvement by lymphoma
- Absolute neutrophil count \>= 1,000/mcL, unless documented bone marrow involvement by lymphoma
- Platelets \>= 75,000/mcL, unless documented bone marrow involvement by lymphoma
- Hemoglobin \>= 8 g/dL, unless documented bone marrow involvement by lymphoma
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement)
- Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)
- Creatinine clearance \>= 30 mL/min/1.73 m\^2 by Cockcroft-Gault
- International normalized ratio (INR) and partial thromboplastin time (aPTT) =\< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
- +6 more criteria
You may not qualify if:
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
- Patients who have previously received gemcitabine plus oxaliplatin therapy
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 2 weeks earlier; however, the following therapies are allowed:
- Hormone-replacement therapy or oral contraceptives
- Herbal therapy \> 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
- Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
- Minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose
- No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
- Treatment with any other investigational agent within 3 weeks prior to cycle 1, day 1
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks prior to cycle 1, day 1
- Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alex F Herrera
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 25, 2017
First Posted
October 26, 2017
Study Start
September 18, 2018
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
April 13, 2026
Record last verified: 2025-12