What side effects are associated with this type of intervention?

Common treatments for Diffuse Large B-Cell Lymphoma (DLBCL) include monoclonal antibodies, kinase inhibitors, and chemotherapy. Monoclonal antibodies like rituximab can cause infusion reactions, particularly during the first cycle, with symptoms such as fever, chills, and respiratory issues. Kinase inhibitors like ibrutinib may lead to bleeding, infections, and atrial fibrillation. Chemotherapy agents such as etoposide, carboplatin, and ifosfamide can result in nausea, vomiting, hair loss, and myelosuppression, increasing the risk of infections and anemia.

What prior FDA approvals exist?

The FDA has approved several treatments for Diffuse Large B-Cell Lymphoma (DLBCL) that involve monoclonal antibodies, kinase inhibitors, and chemotherapy. Rituximab, a monoclonal antibody targeting CD20, is commonly used in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Additionally, ibrutinib, a Bruton's tyrosine kinase inhibitor, has been approved for use in certain cases of DLBCL, particularly in combination with other agents. These treatments aim to interfere with tumor cell growth and proliferation, similar to the combination therapy being studied in the trial involving avelumab, utomilumab, rituximab, ibrutinib, and chemotherapy.

What other types of research exist?

Promising novel alternatives to combination therapy for DLBCL patients include the use of Bruton tyrosine kinase (BTK) inhibitors like ibrutinib, acalabrutinib, and zanubrutinib. These agents have shown efficacy and are better tolerated in some cases compared to traditional therapies. Additionally, ongoing research is exploring the synergy between multiple novel agents, which may offer new treatment strategies in the future.

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Monoclonal Antibodies

Combination Immunotherapy + Chemotherapy for Lymphoma

Phase 1

Waitlist Available

Led By Liana Nikolaenko

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of immune-boosting proteins, a growth-blocking drug, and chemotherapy in patients with certain types of lymphoma that have returned or are resistant to standard treatments. The treatment aims to attack the cancer in multiple ways by boosting the immune system, blocking cancer growth, and killing cancer cells.

Who is the study for?

This trial is for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). They must have a life expectancy over 3 months, be in fairly good health (ECOG score of 0-2), and have adequate organ function. Women should not be pregnant and both genders must agree to use contraception. Exclusions include prior treatments with certain drugs, active infections, other cancers within the last 3 years, severe heart conditions, CNS disease history, and autoimmune diseases.

What is being tested?

The trial tests the combination of monoclonal antibodies avelumab, utomilumab, rituximab with chemotherapy agents ifosfamide, carboplatin etoposide phosphate plus Ibrutinib in patients who've had their lymphoma return or resist treatment. It aims to find safe dosages and observe how well these drugs work together against these types of cancer.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in various organs; infusion-related reactions; blood disorders that can affect clotting or lead to anemia; fatigue; digestive issues like nausea or diarrhea; increased risk of infection due to weakened immunity.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Secondary study objectives

CR rate

Duration of response

Overall response rate

+1 more

Other study objectives

Immunologic and genomic biomarkers

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort II (avelumab, utomilumab, rituximab, ibrutinib)Experimental Treatment5 Interventions

Patients receive rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, and ibrutinib PO QD or rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, utomilumab IV on day 2, and ibrutinib PO QD. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. (Closed as of 12/12/2019)

Group II: Cohort I (avelumab, utomilumab, RICE)Experimental Treatment8 Interventions

Patients receive rituximab IV on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2 or rituximab IV on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on days 2, utomilumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may then undergo autologous hematopoietic stem cell transplantation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Etoposide Phosphate

2011

Completed Phase 2

~160

Ibrutinib

2014

Completed Phase 4

~2060

Autologous Hematopoietic Stem Cell Transplantation

2017

Completed Phase 3

~2090

Ifosfamide

2010

Completed Phase 4

~3140

Avelumab

2017

Completed Phase 2

~2440

Carboplatin

2014

Completed Phase 3

~6120

Rituximab

1999

Completed Phase 4

~2990

Utomilumab

2017

Completed Phase 2

~30

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Diffuse Large B-Cell Lymphoma (DLBCL) include monoclonal antibodies, kinase inhibitors, and chemotherapy. Monoclonal antibodies like rituximab target specific proteins on lymphoma cells, marking them for immune system destruction. Kinase inhibitors such as ibrutinib block enzymes necessary for lymphoma cell growth and survival. Chemotherapy drugs like etoposide, carboplatin, and ifosfamide kill rapidly dividing cells or prevent them from dividing and spreading. These mechanisms are vital for DLBCL patients as they provide multiple strategies to combat the cancer, potentially improving treatment efficacy.