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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments against transformed diffuse large B-cell lymphoma, which has either returned or not responded to previous treatments. It combines immunotherapy, which helps the immune system fight cancer, with chemotherapy, which attacks cancer cells directly. The trial aims to evaluate how well these treatments work together and identify any side effects. Suitable participants have been diagnosed with this specific type of lymphoma and have already tried at least one unsuccessful treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of atezolizumab, gemcitabine, oxaliplatin, and rituximab is generally well-tolerated by patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). Studies indicate that patients can manage this treatment well, even when their condition has returned or is difficult to treat.

While side effects may occur, they are common with cancer treatments. Early studies showed promising results, suggesting this treatment may be effective without causing severe side effects. Researchers continue to study this combination to better understand its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for diffuse large B-cell lymphoma because it includes atezolizumab, which is an immunotherapy drug that helps the immune system recognize and attack cancer cells. Unlike standard treatments that primarily rely on chemotherapy, this approach introduces atezolizumab to enhance the body’s natural defenses alongside traditional chemo agents like gemcitabine and oxaliplatin. This combination aims to improve treatment effectiveness by targeting cancer cells more precisely and potentially reducing the likelihood of disease progression.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

Research has shown that combining atezolizumab with chemotherapy may help treat relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). In this trial, participants will receive a combination of atezolizumab with the chemotherapy drugs in R-GemOx, which previous studies have found to be safe and effective in similar situations. Gemcitabine and oxaliplatin, the chemotherapy drugs, kill cancer cells or stop them from growing. Rituximab, another part of this treatment, attaches to cancer cells, helping the immune system attack them. Together, these treatments aim to boost the body's ability to find and destroy cancer cells. ^{3 4 6 7 8}

Who Is on the Research Team?

Alex F. Herrera

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/14/3530/536801/Atezolizumab-consolidation-in-patients-with-high

Atezolizumab consolidation in patients with high-risk diffuse ... Atezolizumab consolidation in high-risk patients with DLBCL raised 2-year DFS to 87.9% and OS to 96.3%, surpassing historical outcomes.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12274673/

Atezolizumab consolidation in patients with high-risk diffuse ... Atezolizumab consolidation in high-risk patients with DLBCL raised 2-year DFS to 87.9% and OS to 96.3%, surpassing historical outcomes.

3. ajmc.com ajmc.com/view/atezolizumab-immunogenic-chemotherapy-combination-shows-promise-for-dlbcl-treatment

Atezolizumab, Immunogenic Chemotherapy Combination ... Atezolizumab combined with R-GemOx shows favorable safety and efficacy in relapsed/refractory DLBCL, especially in transformed FL cases. The ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10125909/

Safety and efficacy of atezolizumab with rituximab and CHOP ... Atezo–R-CHOP appeared to improve CR rates compared with historical controls but not so much as to warrant further study.

5. haematologica.org haematologica.org/article/view/11691

Atezolizumab combined with immunogenic salvage ... Patients with R/R transformed DLBCL have a poor prognosis, with an estimated 4-year event free survival and overall survival of 27% and 39%, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03321643

Testing the Addition of an Immunotherapy Agent, Atezolizumab ... ... trial studies the side effects of atezolizumab, gemcitabine, oxaliplatin ... (Gemcitabine-Oxaliplatin) and Rituximab for Transformed Diffuse Large B-Cell Lymphoma.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39021209

Atezolizumab combined with immunogenic salvage ... We evaluated the safety and efficacy of atezolizumab plus rituximab and GemOx (R-GemOx+Atezo) in R/R transformed DLBCL, including Richter transformation.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121033814

Atezolizumab Combined with Immunogenic Salvage ... We evaluated the addition of the PD-L1 inhibitor, atezolizumab, to immunogenic chemoimmunotherapy, rituximab with gemcitabine and oxaliplatin (R ...