Atezolizumab + Chemo-Immunotherapy for Diffuse Large B-Cell Lymphoma

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Transplantation, CNS involvement, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 33

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 2 weeks before starting the study, and certain immunosuppressive medications must be stopped 2 weeks prior. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Atezolizumab + Chemo-Immunotherapy for Diffuse Large B-Cell Lymphoma?

Research shows that adding rituximab to chemotherapy significantly improves survival in patients with diffuse large B-cell lymphoma (DLBCL). This suggests that combining rituximab with other drugs, like those in the Atezolizumab + Chemo-Immunotherapy regimen, could also be effective. ^{1 2 3 4 5}

Is the combination of Atezolizumab and chemotherapy safe for humans?

Atezolizumab, used in combination with other treatments, has been associated with immune-related side effects like skin rashes, thyroid issues, and lung inflammation, with severe cases being less common. In a study, most patients experienced some side effects, and there were rare instances of serious events like pneumonia and kidney injury. Overall, while generally considered safe, it can cause significant side effects in some individuals. ^{6 7 8 9 10}

How is the drug Atezolizumab + Chemo-Immunotherapy unique for treating diffuse large B-cell lymphoma?

This treatment combines atezolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy drugs gemcitabine and oxaliplatin, and the antibody rituximab, which targets specific cancer cells. This combination aims to enhance the immune response and improve outcomes for patients with diffuse large B-cell lymphoma, offering a novel approach compared to traditional chemotherapy alone. ^{5 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Alex F. Herrera

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

Adults over 18 with relapsed or refractory transformed diffuse large B-cell lymphoma, including those who have had it change from a less aggressive form or Richter transformation. Participants need to have previously tried at least one treatment and should not be severely ill (ECOG <=2). They must not be pregnant, agree to use contraception, and cannot have certain health conditions like severe allergies, recent infections, or organ transplants.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

I can take care of myself but might not be able to do heavy physical work.

My lymphoma has changed into a more aggressive type known as DLBCL.

Exclusion Criteria

Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

I have a significant liver condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive rituximab, gemcitabine, and oxaliplatin every 2 weeks. Starting cycle 2, atezolizumab is added. Treatment repeats every 14 days for cycle 1 and every 28 days for up to 4 cycles.

Up to 16 weeks

Bi-weekly visits for drug administration and assessments

Maintenance

Patients receive rituximab and atezolizumab every 3 weeks. Monitoring includes CT, PET-CT, MRI, and biopsies.

Ongoing every 3 weeks

Every 3 weeks for drug administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 1 year

Follow-up at 30 days, then every 6 months

Treatment Details

Interventions

• Atezolizumab
• Gemcitabine
• Oxaliplatin
• Rituximab

Trial Overview The trial is testing the combination of Atezolizumab (an immunotherapy drug) with standard chemo-immunotherapy drugs Rituximab, Gemcitabine, and Oxaliplatin in patients whose lymphoma has returned or hasn't responded to treatment. It aims to see if this mix can better help the immune system fight cancer by stopping tumor growth and spread.

Participant Groups

Group I: Treatment (rituximab, gemcitabine, oxaliplatin, atezolizumab) Experimental Treatment 10 Interventions

INDUCTION 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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Rituximab combined with Bruton tyrosine kinase inhibitors (BTKis) shows potential efficacy in treating elderly patients with diffuse large B-cell lymphoma (DLBCL), based on a case study of two patients.

The treatment involved an initial two courses of the R-miniCHOP chemotherapy regimen followed by the combination therapy, suggesting a new strategy for managing DLBCL in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports. Zhang, CJ., Zhao, ML.[2023]

The combination treatment of epratuzumab and rituximab with standard CHOP chemotherapy (ER-CHOP) was feasible for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), with a high overall response rate of 87% and a complete response rate of 67% among 15 patients.

Despite a high incidence of grade 3 or 4 neutropenia (93% of patients), there were no severe infusion-related toxicities, and the treatment showed promising survival rates with 1-year progression-free survival (PFS) at 93% and overall survival (OS) at 100% at a median follow-up of 30 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated, diffuse large B-cell lymphoma. Micallef, IN., Kahl, BS., Maurer, MJ., et al.[2017]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a meta-analysis of 46 studies involving 12,808 cancer patients treated with anti-PD-1/PD-L1 agents, the overall incidence of immune-related adverse events (irAEs) was found to be 26.82%, with severe irAEs occurring in 6.10% of patients.

The types of irAEs varied by organ system and were influenced by the specific drug and cancer type, but the occurrence of these adverse events was not related to the dosage of the PD-1 inhibitors, indicating a need for careful monitoring regardless of treatment levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. Wang, PF., Chen, Y., Song, SY., et al.[2022]

Atezolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, can cause rare but serious immune-related adverse events (irAEs) such as acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP).

In a case study of a patient receiving atezolizumab, the development of AKI and ITP occurred one week after treatment initiation, but with appropriate management including IVIG and steroids, the patient's condition improved and was discharged for routine follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. Yılmaz, A., Mirili, C., Bilici, M., et al.[2022]

Recent advancements in therapies for diffuse large B-cell lymphoma (DLBCL) include new agents like polatuzumab combined with bendamustine and rituximab, which are non-cytotoxic and aim to improve patient outcomes.

The approval of CAR-T cell therapies and ongoing development of bispecific antibodies and antibody drug conjugates suggest a promising future for targeted combination therapies in treating B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma: new targets and novel therapies. Cheson, BD., Nowakowski, G., Salles, G.[2022]

The combination of obinutuzumab and atezolizumab was found to be safe and tolerable in a phase 1b study involving 49 patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), with no new toxicities reported.

The treatment showed preliminary efficacy, achieving a 54% objective response rate in the FL cohort and a 17% response rate in the DLBCL cohort, with median progression-free survival of 9 months for FL and 3 months for DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. Palomba, ML., Till, BG., Park, SI., et al.[2022]

In a study involving 80 patients from the LOTIS-2 trial, loncastuximab tesirine (Lonca) demonstrated a significantly higher overall response rate (53.4%) compared to chemoimmunotherapy (CIT) treatments (40.3%) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Lonca also showed improved overall survival, with a median survival of 10.8 months compared to 6.4 months for CIT, indicating it may be a more effective treatment option for patients with R/R DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Hamadani, M., Chen, L., Song, Y., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated, diffuse large B-cell lymphoma. [2017]

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Atezolizumab: First Global Approval. [2019]

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Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. [2022]

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Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis. [2022]

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A phase-II study of atezolizumab in combination with obinutuzumab or rituximab for relapsed or refractory mantle cell or marginal zone lymphoma or Waldenström's macroglobulinemia. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma: new targets and novel therapies. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. [2019]