What is the mechanism of action of this treatment?

The most common treatments for Marginal Zone Lymphoma (MZL) include antibody-drug conjugates (ADCs) like Loncastuximab Tesirine, which targets CD19 on B-cells. ADCs combine the targeting ability of monoclonal antibodies with the cell-killing power of cytotoxic drugs, leading to the internalization and destruction of malignant cells while sparing healthy ones. Other treatments include monoclonal antibodies such as rituximab, targeting CD20, and BTK inhibitors like ibrutinib, which block critical survival pathways in MZL cells. These targeted therapies are crucial for MZL patients as they provide effective treatment options with potentially fewer side effects than traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Marginal Zone Lymphoma, particularly antibody-drug conjugates like Loncastuximab Tesirine, often have side effects including infusion reactions, fatigue, diarrhea, and hematologic toxicities such as neutropenia and thrombocytopenia. Other treatments, such as chemotherapy and immunotherapy, may cause nausea, vomiting, hair loss, increased risk of infection, and organ-specific toxicities.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Marginal Zone Lymphoma (MZL). Notably, Rituximab, an anti-CD20 monoclonal antibody, has been widely used either alone or in combination with chemotherapy. More recently, the FDA approved Bruton’s tyrosine kinase (BTK) inhibitors such as Ibrutinib for MZL patients who have received at least one prior anti-CD20-based therapy. While Loncastuximab Tesirine, an antibody-drug conjugate targeting CD19, is still under investigation, it represents a promising addition to the arsenal of targeted therapies for MZL.

What other types of research exist?

Promising novel alternatives to Loncastuximab Tesirine for Marginal Zone Lymphoma patients include: 1) Zanubrutinib, a BTK inhibitor, which has shown efficacy in MZL. 2) Tazemetostat, an EZH2 inhibitor, particularly for patients with EZH2 mutations. 3) CAR T-cell therapies targeting CD19, which are being explored for various B-cell lymphomas. 4) Bispecific antibodies like Mosunetuzumab, targeting CD20 and CD3, which have shown promise in clinical trials for B-cell lymphomas.

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Monoclonal Antibodies

Loncastuximab Tesirine for Marginal Zone Lymphoma

Phase 2

Recruiting

Led By Izidore Lossos, MD

Research Sponsored by University of Miami

Eligibility Criteria Checklist

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

Must have

Previously received 1 or more lines of systemic therapy, including at least 1 anti-CD20 antibody, with documented progression or failure to achieve CR or PR after the most recent systemic treatment regimen

Subjects with conjunctival EMZL must have conjunctival lesion measures ≥ 1 cm in diameter or multiple lesions

Must not have

Patients with impaired decision-making capacity

Evidence of DLBCL transformation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

Summary

This trial is testing a medication called loncastuximab tesirine in patients with immune cell cancers. The medication works by finding and sticking to cancer cells, then releasing a poison to kill them. Researchers want to see if this treatment is effective and safe for these patients. Loncastuximab tesirine is a recently approved treatment for a type of immune cell cancer that has returned or not responded to previous treatments.

Who is the study for?

This trial is for adults over 18 with Marginal Zone Lymphoma who've had at least one prior systemic therapy including an anti-CD20 antibody. They should have measurable disease or specific criteria met for non-measurable disease, and be able to undergo biopsies if needed. Key exclusions include recent cancer treatments, other malignancies within the last 3 years, certain heart conditions, liver cirrhosis, autoimmune disorders requiring strong immunosuppression, active infections or HIV/HBV/HCV infection.

What is being tested?

The study tests two doses of Loncastuximab tesirine (150 µg/Kg and 75µg/Kg) in patients with relapsed/refractory Marginal Zone Lymphoma to evaluate its effectiveness and safety. It's an open-label trial meaning everyone knows which treatment they're getting.

What are the potential side effects?

Potential side effects of Loncastuximab tesirine may include symptoms related to infusion reactions like fever or chills, fatigue, changes in blood counts leading to increased risk of infections or bleeding problems, liver enzyme alterations suggesting possible liver damage.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I've had treatment including an anti-CD20 antibody for my condition but it didn't fully work.

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I have a conjunctival eye lesion that is at least 1 cm wide or I have multiple lesions.

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My cancer is a type of marginal zone lymphoma.

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My cancer can be seen on scans.

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My skin lesion is at least 1.5 cm wide or I have multiple skin lesions.

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My stomach cancer's type and stage are confirmed by biopsy.

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I can take care of myself and am up and about more than half of my waking hours.

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I am willing to undergo a biopsy of my lymph node or tissue.

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My spleen cancer has spread to my bone marrow, confirmed by tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am unable to make my own medical decisions.

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My lymphoma has changed into a more aggressive form.

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I do not have heart failure, uncontrolled heart rhythm problems, recent stroke, severe liver disease, or autoimmune disorders.

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I am not currently receiving any cancer treatments.

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I have hepatitis B or C.

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I have recently had a stem cell transplant.

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I am HIV positive.

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I have no ongoing side effects from previous cancer treatments.

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I have a long-term or currently active infection.

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I have had brain lymphoma or cancer spread to the lining of my brain and spinal cord.

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I have been treated with anti-CD19 therapy before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Complete Response (CR) rate of Loncastuximab tesirine in relapsed/refractory at 12 months

Complete Response (CR) rate of Loncastuximab tesirine in relapsed/refractory at 6 months

Secondary study objectives

Duration of Response (DOR)

Number of Treatment Related Toxicities

Overall response rate (ORR) at 12 months

+5 more

Trial Design

1Treatment groups

Experimental Treatment

Group I: Loncastuximab tesirine Cycles 1-6Experimental Treatment2 Interventions

Patients will be treated with loncastuximab tesirine for a total of 6 cycles on Day 1 (+/-3) of each 21 day (3 week) cycle. The total duration of treatment is approximately 18 weeks (4.5 months)

0 / 20Eligibility criteria met

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 Marginal Zone Lymphoma (MZL) include antibody-drug conjugates (ADCs) like Loncastuximab Tesirine, which targets CD19 on B-cells. ADCs combine the targeting ability of monoclonal antibodies with the cell-killing power of cytotoxic drugs, leading to the internalization and destruction of malignant cells while sparing healthy ones. Other treatments include monoclonal antibodies such as rituximab, targeting CD20, and BTK inhibitors like ibrutinib, which block critical survival pathways in MZL cells. These targeted therapies are crucial for MZL patients as they provide effective treatment options with potentially fewer side effects than traditional chemotherapy.