What side effects are associated with this type of intervention?

CAR-T cell therapies, such as Zamtocabtagene Autoleucel, used in the treatment of CNS Lymphoma, are associated with several significant side effects. These include cytokine release syndrome (CRS), which can present with high fever, flu-like symptoms, hypotension, and mental status changes, and can be life-threatening. Neurologic toxicities, such as confusion, seizures, and encephalopathy, are also common and can be severe. Other side effects include prolonged cytopenias, serious infections, hypersensitivity reactions, prolonged hypogammaglobulinemia, and the risk of secondary malignancies.

What prior FDA approvals exist?

The FDA has approved several CAR-T cell therapies targeting CD19 for B-cell malignancies, which are relevant to the treatment of CNS Lymphoma. Notably, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) are approved for certain types of relapsed or refractory large B-cell lymphomas. These therapies involve modifying a patient's T cells to target and kill CD19-expressing B cells, similar to the investigational zamtocabtagene autoleucel being studied for diffuse large B cell lymphoma (DLBCL). While specific approvals for CNS Lymphoma are limited, these CAR-T therapies represent a significant advancement in treating B-cell malignancies, including potential applications in CNS involvement.

What other types of research exist?

Promising alternatives to Zamtocabtagene Autoleucel for CNS Lymphoma patients include other CAR-T cell therapies such as Lisocabtagene Maraleucel and Tisagenlecleucel, which also target CD19 on B cells. Additionally, novel immunotherapies like immune checkpoint inhibitors (e.g., Pembrolizumab, Nivolumab) and bispecific T-cell engagers (BiTEs) such as Blinatumomab are being explored for their efficacy in lymphomas with CNS involvement.

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CAR T-cell Therapy

Cell Therapy for Non-Hodgkin's Lymphoma

Phase 2

Recruiting

Research Sponsored by Miltenyi Biomedicine GmbH

Eligibility Criteria Checklist

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

Must have

Age > 18 years

Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification

Must not have

Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease

Unable to give informed consent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment where a patient's own immune cells are enhanced to fight difficult-to-treat lymphoma. It targets patients whose cancer hasn't responded to at least two other treatments. The modified cells aim to better recognize and attack the cancer. This new method improves the ability of the patient's immune cells to find and destroy cancer cells.

Who is the study for?

Adults with Diffuse Large B-Cell Lymphoma (DLBCL) who have tried at least two other treatments without success can join this study. They should not be candidates for a stem cell transplant or must have chosen not to undergo one. Participants need to be over 18, in fairly good health otherwise, and able to follow birth control guidelines during the trial.

What is being tested?

The clinical trial is testing MB-CART2019.1 cells' effectiveness and safety in treating DLBCL that has resisted previous therapies. It's an open-label phase II study, meaning everyone gets the treatment and knows what it is, focusing on how well these cells work and their impact on patients.

What are the potential side effects?

While specific side effects of MB-CART2019.1 are not listed here, similar CAR-T therapies often cause flu-like symptoms, fatigue, difficulty breathing, heart issues, confusion or trouble speaking (neurotoxicity), low blood counts leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I am older than 18 years.

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My diagnosis is DLBCL or a related type, confirmed by a lab test.

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I am not suspected to have lymphoma in my brain or spinal cord.

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My kidneys are functioning well, with a creatinine clearance over 60 mL/min.

Exclusion Criteria

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

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I have an autoimmune disease affecting my nervous system.

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I am unable to understand and agree to the study's procedures and risks.

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My CLL has transformed into a more aggressive type of lymphoma.

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I do not have any ongoing serious infections.

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I haven't had seizures or taken seizure medications in the last year.

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My cancer is a type of lymphoma that affects the brain.

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

Overall Response Rate

Secondary study objectives

Best Overall Response

Complete Response Rate

Correlation of tumor CD19 and CD20 antigen expression with disease progression and relapse

+10 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Single, open labelExperimental Treatment4 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fludarabine

2012

Completed Phase 4

~1860

Bendamustine

2015

Completed Phase 3

~3230

Cyclophosphamide

2010

Completed Phase 4

~2310

0 / 10Eligibility 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 Central Nervous System (CNS) Lymphoma include high-dose methotrexate-based chemotherapy, rituximab, and CAR-T cell therapy. High-dose methotrexate works by inhibiting dihydrofolate reductase, leading to the disruption of DNA synthesis and cell replication, which is crucial for targeting rapidly dividing lymphoma cells. Rituximab is a monoclonal antibody that targets CD20 on B cells, leading to their destruction through mechanisms such as antibody-dependent cellular cytotoxicity and complement activation. CAR-T cell therapy, such as zamtocabtagene autoleucel, involves modifying a patient's T cells to express a chimeric antigen receptor (CAR) that specifically targets CD19 on B cells, leading to direct cytotoxicity against the lymphoma cells. These mechanisms are vital for CNS Lymphoma patients as they provide targeted approaches to eliminate malignant cells while sparing normal tissues, potentially leading to better outcomes and fewer side effects compared to traditional therapies.